De Martino, M., Rathmell, J. C., Galluzzi, L. & Vanpouille-Box, C. Cancer cell metabolism and antitumour immunity. Nat. Rev. Immunol. 24, 654–669 (2024).
Google Scholar
Tzouanas, C. N. et al. Hepatic adaptation to chronic metabolic stress primes tumorigenesis. Cell 189, 435–460.e28 (2026).
Google Scholar
Lee, J. M., Hammarén, H. M., Savitski, M. M. & Baek, S. H. Control of protein stability by post-translational modifications. Nat. Commun. 14, 201 (2023).
Google Scholar
Chen, Y. et al. O-GlcNAcylation determines the translational regulation and phase separation of YTHDF proteins. Nat. Cell Biol. 25, 1676–1690 (2023).
Google Scholar
Yang, Z. et al. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma. Nat. Metab. 5, 61–79 (2023).
Google Scholar
Feng, F. et al. Lactylome analysis unveils lactylation-dependent mechanisms of stemness remodeling in the liver cancer stem cells. Adv. Sci. 11, e2405975 (2024).
Google Scholar
Levene, P. A. & Alsberg, C. L. The cleavage products of vitellin. J. Biol. Chem. 2, 127–133 (1906).
Google Scholar
Fischer, E. H. & Krebs, E. G. Conversion of phosphorylase b to phosphorylase a in muscle extracts. J. Biol. Chem. 216, 121–132 (1955).
Google Scholar
Krebs, E. G. & Fischer, E. H. The phosphorylase b to a converting enzyme of rabbit skeletal muscle. Biochim. Biophys. Acta 20, 150–157 (1956).
Google Scholar
Krebs, E. G., Kent, A. B. & Fischer, E. H. The muscle phosphorylase b kinase reaction. J. Biol. Chem. 231, 73–83 (1958).
Google Scholar
DeLange, R. J., Kemp, R. G., Riley, W. D., Cooper, R. A. & Krebs, E. G. Activation of skeletal muscle phosphorylase kinase by adenosine triphosphate and adenosine 3′, 5′-monophosphate. J. Biol. Chem. 243, 2200–2208 (1968).
Google Scholar
Walsh, D. A., Perkins, J. P. & Krebs, E. G. An adenosine 3′, 5′-monophosphate-dependant protein kinase from rabbit skeletal muscle. J. Biol. Chem. 243, 3763–3765 (1968).
Google Scholar
Goldstein, G. et al. Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc. Natl. Acad. Sci. USA 72, 11–15 (1975).
Google Scholar
Goldknopf, I. L. & Busch, H. Isopeptide linkage between nonhistone and histone 2A polypeptides of chromosomal conjugate-protein A24. Proc. Natl. Acad. Sci. USA 74, 864–868 (1977).
Google Scholar
Schmidt, M. F. & Schlesinger, M. J. Fatty acid binding to vesicular stomatitis virus glycoprotein: a new type of post-translational modification of the viral glycoprotein. Cell 17, 813–819 (1979).
Google Scholar
Schmidt, M. F., Bracha, M. & Schlesinger, M. J. Evidence for covalent attachment of fatty acids to Sindbis virus glycoproteins. Proc. Natl. Acad. Sci. USA 76, 1687–1691 (1979).
Google Scholar
Kamiya, Y. et al. Structure of rhodotorucine A, a novel lipopeptide, inducing mating tube formation in Rhodosporidiumtoruloides. Biochem. Biophys. Res. Commun. 83, 1077–1083 (1978).
Google Scholar
Wolda, S. L. & Glomset, J. A. Evidence for modification of lamin B by a product of mevalonic acid. J. Biol. Chem. 263, 5997–6000 (1988).
Google Scholar
Carr, S. A., Biemann, K., Shoji, S., Parmelee, D. C. & Titani, K. n-Tetradecanoyl is the NH2-terminal blocking group of the catalytic subunit of cyclic AMP-dependent protein kinase from bovine cardiac muscle. Proc. Natl. Acad. Sci. USA 79, 6128–6131 (1982).
Google Scholar
Brockhausen, I. et al. Specificity of O-glycosylation by bovine colostrum UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase using synthetic glycopeptide substrates. Glycoconj. J. 13, 849–856 (1996).
Google Scholar
Torres, C. R. & Hart, G. W. Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. Evidence for O-linked GlcNAc. J. Biol. Chem. 259, 3308–3317 (1984).
Google Scholar
Kumar, S., Tomooka, Y. & Noda, M. Identification of a set of genes with developmentally down-regulated expression in the mouse brain. Biochem. Biophys. Res. Commun. 185, 1155–1161 (1992).
Google Scholar
Kamitani, T., Kito, K., Nguyen, H. P. & Yeh, E. T. Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein. J. Biol. Chem. 272, 28557–28562 (1997).
Google Scholar
Osaka, F. et al. A new NEDD8-ligating system for cullin-4A. Genes Dev 12, 2263–2268 (1998).
Google Scholar
Mahajan, R., Delphin, C., Guan, T., Gerace, L. & Melchior, F. A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88, 97–107 (1997).
Google Scholar
Matunis, M. J., Coutavas, E. & Blobel, G. A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex. J. Cell Biol. 135, 1457–1470 (1996).
Google Scholar
Komatsu, M. et al. A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier. EMBO J. 23, 1977–1986 (2004).
Google Scholar
Mann, M. et al. Analysis of protein phosphorylation using mass spectrometry: deciphering the phosphoproteome. Trends Biotechnol. 20, 261–268 (2002).
Google Scholar
Aebersold, R. & Mann, M. Mass spectrometry-based proteomics. Nature 422, 198–207 (2003).
Google Scholar
Brown, M. P. et al. Knowledge-based analysis of microarray gene expression data by using support vector machines. Proc. Natl. Acad. Sci. USA 97, 262–267 (2000).
Google Scholar
Liu, K. et al. 5-HT orchestrates histone serotonylation and citrullination to drive neutrophil extracellular traps and liver metastasis. J. Clin. Investig. 135, e183544 (2025).
Google Scholar
Walther, D. J. et al. Serotonylation of small GTPases is a signal transduction pathway that triggers platelet α-granule release. Cell 115, 851–862 (2003).
Google Scholar
Chen, Y. et al. Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol. Cell. Proteomics 6, 812–819 (2007).
Google Scholar
Tan, M. et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146, 1016–1028 (2011).
Google Scholar
Zhang, Z. et al. Identification of lysine succinylation as a new post-translational modification. Nat. Chem. Biol. 7, 58–63 (2011).
Google Scholar
Peng, C. et al. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell. Proteomics 10, (2011).
Tan, M. et al. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 19, 605–617 (2014).
Google Scholar
Dai, L. et al. Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark. Nat. Chem. Biol. 10, 365–370 (2014).
Google Scholar
Xie, Z. et al. Metabolic regulation of gene expression by histone lysine β-hydroxybutyrylation. Mol. Cell 62, 194–206 (2016).
Google Scholar
Zhang, D. et al. Metabolic regulation of gene expression by histone lactylation. Nature 574, 575–580 (2019).
Google Scholar
He, X. et al. Lysine vitcylation is a vitamin C-derived protein modification that enhances STAT1-mediated immune response. Cell 188, 1858–1877.e21 (2025).
Google Scholar
Vannam, R. et al. Targeted degradation of the enhancer lysine acetyltransferases CBP and p300. Cell Chem. Biol. 28, 503–514.e12 (2021).
Google Scholar
Wang, Y. et al. The lncRNA PVT1 regulates nasopharyngeal carcinoma cell proliferation via activating the KAT2A acetyltransferase and stabilizing HIF-1. Cell Death Differ. 27, 695–710 (2020).
Google Scholar
Nguyen, M. U. et al. KAT2A and KAT2B prevent double-stranded RNA accumulation and interferon signaling to maintain intestinal stem cell renewal. Sci. Adv. 10, eadl1584 (2024).
Google Scholar
Baell, J. B. et al. Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth. Nature 560, 253–257 (2018).
Google Scholar
Guhathakurta, S. et al. COX17 acetylation via MOF-KANSL complex promotes mitochondrial integrity and function. Nat. Metab. 5, 1931–1952 (2023).
Google Scholar
Haberland, M., Montgomery, R. L. & Olson, E. N. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat. Rev. Genet. 10, 32–42 (2009).
Google Scholar
Imai, S., Armstrong, C. M., Kaeberlein, M. & Guarente, L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403, 795–800 (2000).
Google Scholar
Filippakopoulos, P. et al. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell 149, 214–231 (2012).
Google Scholar
Song, L. et al. Hotspot mutations in the structured ENL YEATS domain link aberrant transcriptional condensates and cancer. Mol. Cell 82, 4080–4098.e12 (2022).
Google Scholar
Sanchez, R. & Zhou, M.-M. The PHD finger: a versatile epigenome reader. Trends Biochem. Sci. 36, 364–372 (2011).
Google Scholar
Wellen, K. E. et al. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324, 1076–1080 (2009).
Google Scholar
He, W., Li, Q. & Li, X. Acetyl-CoA regulates lipid metabolism and histone acetylation modification in cancer. Biochim. Biophys. Acta Rev. Cancer 1878, 188837 (2023).
Google Scholar
Zhu, R. et al. ACSS2 acts as a lactyl-CoA synthetase and couples KAT2A to function as a lactyltransferase for histone lactylation and tumor immune evasion. Cell Metab. 37, 361–376.e7 (2025).
Google Scholar
Liu, R. et al. Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis. Cell Metab. 37, 377–394.e9 (2025).
Google Scholar
Xie, B. et al. KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis. Proc. Natl. Acad. Sci. USA 121, e2314128121 (2024).
Google Scholar
Chen, H. et al. NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance. Nature 631, 663–669 (2024).
Google Scholar
Zong, Z. et al. Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell 187, 2375–2392.e33 (2024).
Google Scholar
Li, H. et al. AARS1 and AARS2 sense L-lactate to regulate cGAS as global lysine lactyltransferases. Nature 634, 1229–1237 (2024).
Google Scholar
Moreno-Yruela, C. et al. Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci. Adv. 8, eabi6696 (2022).
Google Scholar
Du, R. et al. Sirtuin 1/sirtuin 3 are robust lysine delactylases and sirtuin 1-mediated delactylation regulates glycolysis. iScience 27, 110911 (2024).
Google Scholar
Jin, J. et al. SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth. EMBO Rep. 24, e56052 (2023).
Google Scholar
Zhai, G. et al. DPF2 reads histone lactylation to drive transcription and tumorigenesis. Proc. Natl. Acad. Sci. USA 121, e2421496121 (2024).
Google Scholar
Li, H., Sun, L., Gao, P. & Hu, H. Lactylation in cancer: current understanding and challenges. Cancer Cell 42, 1803–1807 (2024).
Google Scholar
Huang, H. et al. p300-Mediated lysine 2-hydroxyisobutyrylation regulates glycolysis. Mol. Cell 70, 984 (2018).
Google Scholar
Xu, W. et al. Global profiling of crotonylation on non-histone proteins. Cell Res. 27, 946–949 (2017).
Google Scholar
Kaczmarska, Z. et al. Structure of p300 in complex with acyl-CoA variants. Nat. Chem. Biol. 13, 21–29 (2017).
Google Scholar
Yang, G. et al. Histone acetyltransferase 1 is a succinyltransferase for histones and non-histones and promotes tumorigenesis. EMBO Rep. 22, e50967 (2021).
Google Scholar
Wang, Y. F. et al. Aspirin modulates succinylation of PGAM1K99 to restrict the glycolysis through NF-κB/HAT1/PGAM1 signaling in liver cancer. Acta Pharmacol. Sin. 44, 211–220 (2023).
Google Scholar
Zhang, J. et al. Antitumorigenic potential of Lactobacillus-derived extracellular vesicles: p53 succinylation and glycolytic reprogramming in intestinal epithelial cells via SIRT5 modulation. Cell Biol. Toxicol. 40, 66 (2024).
Google Scholar
Du, J. et al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334, 806–809 (2011).
Google Scholar
Schjoldager, K. T., Narimatsu, Y., Joshi, H. J. & Clausen, H. Global view of human protein glycosylation pathways and functions. Nat. Rev. Mol. Cell Biol. 21, 729–749 (2020).
Google Scholar
Zielinska, D. F., Gnad, F., Wiśniewski, J. R. & Mann, M. Precision mapping of an in vivo N-glycoproteome reveals rigid topological and sequence constraints. Cell 141, 897–907 (2010).
Google Scholar
Nielsen, M. I. et al. Global mapping of GalNAc-T isoform-specificities and O-glycosylation site-occupancy in a tissue-forming human cell line. Nat. Commun. 13, 6257 (2022).
Google Scholar
Ramírez, A. S. et al. Molecular basis for glycan recognition and reaction priming of eukaryotic oligosaccharyltransferase. Nat. Commun. 13, 7296 (2022).
Google Scholar
Yang, X. & Qian, K. Protein O-GlcNAcylation: emerging mechanisms and functions. Nat. Rev. Mol. Cell Biol. 18, 452–465 (2017).
Google Scholar
Lam, C., Low, J. Y., Tran, P. T. & Wang, H. The hexosamine biosynthetic pathway and cancer: current knowledge and future therapeutic strategies. Cancer Lett. 503, 11–18 (2021).
Google Scholar
Tate, E. W., Soday, L., de la Lastra, A. L., Wang, M. & Lin, H. Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets. Nat. Rev. Cancer 24, 240–260 (2024).
Google Scholar
Hancock, J. F., Paterson, H. & Marshall, C. J. A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane. Cell 63, 133–139 (1990).
Google Scholar
Storck, E. M. et al. Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics. Nat. Chem. 11, 552–561 (2019).
Google Scholar
Wang, H., Xu, X., Wang, J. & Qiao, Y. The role of N-myristoyltransferase 1 in tumour development. Ann. Med. 55, 1422–1430 (2023).
Google Scholar
Lin, D. T. S. & Conibear, E. ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization. eLife 4, e11306 (2015).
Google Scholar
Mesquita, S. et al. Mechanisms and functions of protein S-acylation. Nat. Rev. Mol. Cell Biol. 25, 488–509 (2024).
Google Scholar
Sampson, C. et al. The roles of E3 ubiquitin ligases in cancer progression and targeted therapy. Clin. Transl. Med. 13, e1204 (2023).
Google Scholar
Komander, D. & Rape, M. The ubiquitin code. Annu. Rev. Biochem. 81, 203–229 (2012).
Google Scholar
Liu, F. et al. Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches. Mol. Cancer 23, 148 (2024).
Google Scholar
Rahman, S. & Wolberger, C. Breaking the K48-chain: linking ubiquitin beyond protein degradation. Nat. Struct. Mol. Biol. 31, 216–218 (2024).
Google Scholar
Shi, Q. et al. Role of TOMM34 on NF-κB activation-related hyperinflammation in severely ill patients with COVID-19 and influenza. EBioMedicine 108, 105343 (2024).
Google Scholar
Nespolo, A. et al. USP1 deubiquitinates PARP1 to regulate its trapping and PARylation activity. Sci. Adv. 10, eadp6567 (2024).
Google Scholar
Hou, J. et al. USP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS. Nat. Commun. 12, 2970 (2021).
Google Scholar
Yu, Y. et al. K29-linked ubiquitin signaling regulates proteotoxic stress response and cell cycle. Nat. Chem. Biol. 17, 896–905 (2021).
Google Scholar
Liu, X. et al. Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin-activating enzymes. Nat. Commun. 8, 14286 (2017).
Google Scholar
Walden, H. et al. The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1. Mol. Cell 12, 1427–1437 (2003).
Google Scholar
Lin, X. et al. UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance. Cell Death Dis. 15, 590 (2024).
Google Scholar
Chang, Y. et al. The UBE2F-CRL5ASB11-DIRAS2 axis is an oncogene and tumor suppressor cascade in pancreatic cancer cells. Dev. Cell 59, 1317–1332.e5 (2024).
Google Scholar
Huang, D. T. et al. E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol. Cell 33, 483–495 (2009).
Google Scholar
Schulze-Niemand, E. & Naumann, M. The COP9 signalosome: a versatile regulatory hub of Cullin-RING ligases. Trends Biochem. Sci. 48, 82–95 (2023).
Google Scholar
Baek, K. et al. NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly. Nature 578, 461–466 (2020).
Google Scholar
Shi, L. et al. ROS-mediated up-regulation of SAE1 by Helicobacter pylori promotes human gastric tumor genesis and progression. J. Transl. Med. 22, 148 (2024).
Google Scholar
Chen, H. et al. UBA2 SUMOylates NQO1 and promotes the proliferation of hepatocellular carcinoma by modulating the MAPK pathway. Cancer Sci. 115, 2998–3012 (2024).
Google Scholar
Xiao, J. et al. UBC9 deficiency enhances immunostimulatory macrophage activation and subsequent antitumor T cell response in prostate cancer. J. Clin. Investig. 133, e158352 (2023).
Google Scholar
Lara-Ureña, N., Jafari, V. & García-Domínguez, M. Cancer-associated dysregulation of sumo regulators: proteases and ligases. Int. J. Mol. Sci. 23, 8012 (2022).
Google Scholar
Wu, X. et al. SUMO specific peptidase 3 halts pancreatic ductal adenocarcinoma metastasis via deSUMOylating DKC1. Cell Death Differ. 30, 1742–1756 (2023).
Google Scholar
Chang, H. M. & Yeh, E. T. H. SUMO: from bench to bedside. Physiol. Rev. 100, 1599–1619 (2020).
Google Scholar
Jia, W. et al. Hypoxia-induced RCOR2 promotes macrophage M2 polarization and CD8+ T-cell exhaustion by enhancing LIF transcription in hepatocellular carcinoma. J. Immunother. Cancer 13, e012314 (2025).
Google Scholar
Ye, Z. et al. Enhanced sensitivity and scalability with a Chip-Tip workflow enables deep single-cell proteomics. Nat. Methods 22, 499–509 (2025).
Google Scholar
Cutler, R. et al. Mass spectrometry-based profiling of single-cell histone post-translational modifications to dissect chromatin heterogeneity. Nat. Commun. 16, 11100 (2025).
Google Scholar
Gan, Q. & Fan, C. Orthogonal translation for site-specific installation of post-translational modifications. Chem. Rev. 124, 2805–2838 (2024).
Google Scholar
Eskonen, V., Tong-Ochoa, N., Valtonen, S., Kopra, K. & Härmä, H. Thermal dissociation assay for time-resolved fluorescence detection of protein post-translational modifications. ACS Omega 4, 16501–16507 (2019).
Google Scholar
Cao, C. et al. Deep learning-assisted single-molecule detection of protein post-translational modifications with a biological nanopore. ACS Nano 18, 1504–1515 (2023).
Google Scholar
Meng, Q. et al. Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progression. J. Exp. Clin. Cancer Res. 43, 36 (2024).
Google Scholar
Meng, Q. et al. Human papillomavirus-16 E6 activates the pentose phosphate pathway to promote cervical cancer cell proliferation by inhibiting G6PD lactylation. Redox Biol. 71, 103108 (2024).
Google Scholar
Sun, M. et al. PIKE-A promotes glioblastoma growth by driving PPP flux through increasing G6PD expression mediated by phosphorylation of STAT3. Biochem. Pharmacol. 192, 114736 (2021).
Google Scholar
Sun, M. et al. PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1-mediated cell metabolism. Acta Pharm. Sin. B 13, 157–173 (2023).
Google Scholar
Jin, X. et al. METTL3 confers oxaliplatin resistance through the activation of G6PD-enhanced pentose phosphate pathway in hepatocellular carcinoma. Cell Death Differ. 32, 466–479 (2025).
Google Scholar
Cheng, J. et al. TRIM21 and PHLDA3 negatively regulate the crosstalk between the PI3K/AKT pathway and PPP metabolism. Nat. Commun. 11, 1880 (2020).
Google Scholar
Stacpoole, P. W. Therapeutic targeting of the pyruvate dehydrogenase complex/pyruvate dehydrogenase kinase (PDC/PDK) axis in cancer. J. Natl. Cancer Inst. 109, (2017).
Jiang, Z. et al. PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation-mediated gene expression. Protein Cell 16, 49–63 (2025).
Google Scholar
Qian, X. et al. PTEN suppresses glycolysis by dephosphorylating and inhibiting autophosphorylated PGK1. Mol. Cell 76, 516–527.e7 (2019).
Google Scholar
Li, X. et al. Mitochondria-translocated PGK1 functions as a protein kinase to coordinate glycolysis and the TCA cycle in tumorigenesis. Mol. Cell 61, 705–719 (2016).
Google Scholar
Liu, H. et al. PRMT1-mediated PGK1 arginine methylation promotes colorectal cancer glycolysis and tumorigenesis. Cell Death Dis. 15, 170 (2024).
Google Scholar
Nie, H. et al. O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth. Nat. Commun. 11, 36 (2020).
Google Scholar
Guo, Z. et al. Hypoxia-induced downregulation of PGK1 crotonylation promotes tumorigenesis by coordinating glycolysis and the TCA cycle. Nat. Commun. 15, 6915 (2024).
Google Scholar
Peng, Z. et al. Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer. Nat. Chem. Biol. 21, 59–70 (2025).
Google Scholar
Chen, T. et al. AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis. Nat. Commun. 15, 686 (2024).
Google Scholar
Zhou, Z. et al. ULK1-dependent phosphorylation of PKM2 antagonizes O-GlcNAcylation and regulates the Warburg effect in breast cancer. Oncogene 43, 1769–1778 (2024).
Google Scholar
Zhang, R. et al. HDAC8-dependent deacetylation of PKM2 directs nuclear localization and glycolysis to promote proliferation in hepatocellular carcinoma. Cell Death Dis. 11, 1036 (2020).
Google Scholar
Zhou, Q. et al. GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism. Redox Biol. 56, 102458 (2022).
Google Scholar
Zhang, J. et al. ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment. Mol. Cancer 23, 94 (2024).
Google Scholar
Pan, J. et al. Correction: CHAC1 blockade suppresses progression of lung adenocarcinoma by interfering with glucose metabolism via hijacking PKM2 nuclear translocation. Cell Death Dis. 15, 885 (2024).
Google Scholar
Coassolo, S. et al. Citrullination of pyruvate kinase M2 by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation. Nat. Commun. 12, 1718 (2021).
Google Scholar
Peng, L. et al. PRMT1 promotes Warburg effect by regulating the PKM2/PKM1 ratio in non-small cell lung cancer. Cell Death Dis. 15, 504 (2024).
Google Scholar
Wong, T. L. et al. CRAF methylation by PRMT6 regulates aerobic glycolysis-driven hepatocarcinogenesis via ERK-dependent PKM2 nuclear relocalization and activation. Hepatology 71, 1279–1296 (2020).
Google Scholar
Yu, S., Zang, W., Qiu, Y., Liao, L. & Zheng, X. Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis. Oncogene 41, 46–56 (2022).
Google Scholar
Wang, Y. et al. PKM2 functions as a histidine kinase to phosphorylate PGAM1 and increase glycolysis shunts in cancer. EMBO J. 43, 2368–2396 (2024).
Google Scholar
Xie, F. et al. PRMT5 promotes ovarian cancer growth through enhancing the Warburg effect by methylating ENO1. MedComm 4, e245 (2023).
Google Scholar
Zhu, Q. et al. O-GlcNAcylation of enolase 1 serves as a dual regulator of aerobic glycolysis and immune evasion in colorectal cancer. Proc. Natl. Acad. Sci. USA 121, e2408354121 (2024).
Google Scholar
Fang, Y. et al. SENP1 drives glycolysis and cisplatin resistance in gastric cancer via desumoylating ENO1. J. Exp. Clin. Cancer Res. 44, 285 (2025).
Google Scholar
Li, X. et al. Lysine-222 succinylation reduces lysosomal degradation of lactate dehydrogenase a and is increased in gastric cancer. J. Exp. Clin. Cancer Res. 39, 172 (2020).
Google Scholar
Kwon, O. K. et al. LDHA desuccinylase sirtuin 5 as a novel cancer metastatic stimulator in aggressive prostate cancer. Genom. Proteomics Bioinform. 21, 177–189 (2023).
Google Scholar
Shi, L. et al. LncRNA GLTC targets LDHA for succinylation and enzymatic activity to promote progression and radioiodine resistance in papillary thyroid cancer. Cell Death Differ. 30, 1517–1532 (2023).
Google Scholar
Yang, S. et al. HIF1α/ATF3 partake in PGK1 K191/K192 succinylation by modulating P4HA1/succinate signaling in glioblastoma. Neuro-Oncol 26, 1405–1420 (2024).
Google Scholar
Huangfu, L. et al. The deubiquitinase USP15 drives malignant progression of gastric cancer through glucose metabolism remodeling. J. Exp. Clin. Cancer Res. 43, 235 (2024).
Google Scholar
Hu, C. et al. USP4 promotes PTC progression by stabilizing LDHA and activating the MAPK and AKT signaling pathway. Aging 16, 12850–12865 (2024).
Google Scholar
Sun, X. et al. The tumor suppressor Parkin exerts anticancer effects through regulating mitochondrial GAPDH activity. Oncogene 43, 3215–3226 (2024).
Google Scholar
Shangguan, X. et al. SUMOylation controls the binding of hexokinase 2 to mitochondria and protects against prostate cancer tumorigenesis. Nat. Commun. 12, 1812 (2021).
Google Scholar
Tantai, J., Pan, X., Chen, Y., Shen, Y. & Ji, C. TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells. Cell Death Dis. 13, 285 (2022).
Google Scholar
Wang, J. et al. A non-metabolic function of hexokinase 2 in small cell lung cancer: promotes cancer cell stemness by increasing USP11-mediated CD133 stability. Cancer Commun. 42, 1008–1027 (2022).
Google Scholar
Jiang, X. et al. KRASG12D-driven pentose phosphate pathway remodeling imparts a targetable vulnerability synergizing with MRTX1133 for durable remissions in PDAC. Cell Rep. Med. 6, 101966 (2025).
Google Scholar
Xia, T., Meng, L., Xu, G., Sun, H. & Chen, H. TRIM33 promotes glycolysis through regulating P53 K48-linked ubiquitination to promote esophageal squamous cell carcinoma growth. Cell Death Dis. 15, 740 (2024).
Google Scholar
Chen, S. et al. Inhibition of KIF20A enhances the immunotherapeutic effect of hepatocellular carcinoma by enhancing c-Myc ubiquitination. Cancer Lett. 598, 217105 (2024).
Google Scholar
Deng, Z. et al. DLGAP5 enhances bladder cancer chemoresistance by regulating glycolysis through MYC stabilization. Theranostics 15, 2375–2392 (2025).
Google Scholar
Lin, Y. et al. Phosphorylation determines the glucose metabolism reprogramming and tumor-promoting activity of sine oculis homeobox 1. Signal Transduct. Target. Ther. 9, 337 (2024).
Google Scholar
Ling, S. et al. USP22 promotes hypoxia-induced hepatocellular carcinoma stemness by a HIF1α/USP22 positive feedback loop upon TP53 inactivation. Gut 69, 1322–1334 (2020).
Google Scholar
Zhang, R. et al. UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL. Clin. Mol. Hepatol. 30, 771–792 (2024).
Google Scholar
Nan, Y. et al. OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition. Proc. Natl. Acad. Sci. USA 121, e2315348121 (2024).
Google Scholar
Li, F. et al. Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma. Mol. Cancer 23, 90 (2024).
Google Scholar
Chen, M. et al. NUSAP1-LDHA-glycolysis-lactate feedforward loop promotes Warburg effect and metastasis in pancreatic ductal adenocarcinoma. Cancer Lett. 567, 216285 (2023).
Google Scholar
Guan, B. et al. Peritumoral colonic epithelial cell-derived GDF15 sustains colorectal cancer via regulation of glycolysis and histone lactylation. Nat. Aging 5, 2449–2465 (2025).
Google Scholar
Hong, H. et al. ABCF1-K430-Lactylation promotes HCC malignant progression via transcriptional activation of HIF1 signaling pathway. Cell Death Differ. 32, 613–631 (2025).
Google Scholar
Tong, Y. et al. KAT2A succinyltransferase activity-mediated 14-3-3ζ upregulation promotes β-catenin stabilization-dependent glycolysis and proliferation of pancreatic carcinoma cells. Cancer Lett. 469, 1–10 (2020).
Google Scholar
Duan, W. et al. Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis. J. Transl. Med. 21, 547 (2023).
Google Scholar
Chen, Y. et al. Metabolic regulation of homologous recombination repair by MRE11 lactylation. Cell 187, 294–311.e21 (2024).
Google Scholar
Li, G. et al. Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma. Cell Metab. 36, 1696–1710.e10 (2024).
Google Scholar
Zheng, B. et al. High sugar induced RCC2 lactylation drives breast cancer tumorigenicity through upregulating MAD2L1. Adv. Sci. 12, e2415530 (2025).
Google Scholar
Wu, J. et al. KAT2A-driven succinylation of SRSF11 enforces spliceosome-mediated RAD52 splicing to promote homologous recombination and radioresistance in hepatocellular carcinoma. Signal Transduct. Target. Ther. 10, 364 (2025).
Google Scholar
Wang, H. et al. The OGT-c-Myc-PDK2 axis rewires the TCA cycle and promotes colorectal tumor growth. Cell Death Differ. 31, 1157–1169 (2024).
Google Scholar
Chu, Y. et al. O-GlcNAcylation of SIX1 enhances its stability and promotes hepatocellular carcinoma proliferation. Theranostics 10, 9830–9842 (2020).
Google Scholar
Zhang, N. et al. FBXO31-mediated ubiquitination of OGT maintains O-GlcNAcylation homeostasis to restrain endometrial malignancy. Nat. Commun. 16, 1274 (2025).
Google Scholar
Lin, L. et al. CARM1-mediated OGT arginine methylation promotes non-small cell lung cancer glycolysis by stabilizing OGT. Cell Death Dis. 15, 927 (2024).
Google Scholar
Liu, R. et al. O-GlcNAc modified-TIP60/KAT5 is required for PCK1 deficiency-induced HCC metastasis. Oncogene 40, 6707–6719 (2021).
Google Scholar
Tuo, L. et al. PCK1 negatively regulates cell cycle progression and hepatoma cell proliferation via the AMPK/p27Kip1 axis. J. Exp. Clin. Cancer Res. 38, 50 (2019).
Google Scholar
Xiang, J. et al. Gluconeogenic enzyme PCK1 deficiency promotes CHK2 O-GlcNAcylation and hepatocellular carcinoma growth upon glucose deprivation. J. Clin. Investig. 131, e144703 (2021). 144703.
Google Scholar
Shan, C. et al. 4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis. Cell Death Dis. 10, 525 (2019).
Google Scholar
Li, Y. et al. AMPK-dependent phosphorylation of HDAC8 triggers PGM1 expression to promote lung cancer cell survival under glucose starvation. Cancer Lett. 478, 82–92 (2020).
Google Scholar
Bi, L. et al. HDAC11 regulates glycolysis through the LKB1/AMPK signaling pathway to maintain hepatocellular carcinoma stemness. Cancer Res. 81, 2015–2028 (2021).
Google Scholar
Ding, C. H. et al. PRMT3 drives PD-L1-mediated immune escape through activating PDHK1-regulated glycolysis in hepatocellular carcinoma. Cell Death Dis. 16, 158 (2025).
Google Scholar
Zhang, C. et al. H3K18 lactylation potentiates immune escape of non-small cell lung cancer. Cancer Res. 84, 3589–3601 (2024).
Google Scholar
Huang, Z. W. et al. STAT5 promotes PD-L1 expression by facilitating histone lactylation to drive immunosuppression in acute myeloid leukemia. Signal Transduct. Target. Ther. 8, 391 (2023).
Google Scholar
Ma, Z. et al. Histone lactylation-driven B7-H3 expression promotes tumor immune evasion. Theranostics 15, 2338–2359 (2025).
Google Scholar
Zhang, W. et al. Hexokinase HK3-mediated O-GlcNAcylation of EP300: a key regulator of PD-L1 expression and immune evasion in ccRCC. Cell Death Dis. 15, 613 (2024).
Google Scholar
Xu, W. et al. Hexokinase 3 dysfunction promotes tumorigenesis and immune escape by upregulating monocyte/macrophage infiltration into the clear cell renal cell carcinoma microenvironment. Int. J. Biol. Sci. 17, 2205–2222 (2021).
Google Scholar
Guo, D. et al. Aerobic glycolysis promotes tumor immune evasion by hexokinase2-mediated phosphorylation of IκBα. Cell Metab. 34, 1312–1324.e6 (2022).
Google Scholar
Lin, J. et al. Glycolytic enzyme HK2 promotes PD-L1 expression and breast cancer cell immune evasion. Front. Immunol. 14, 1189953 (2023).
Google Scholar
Tong, Y. et al. Hexokinase 2 nonmetabolic function-mediated phosphorylation of IκBα enhances pancreatic ductal adenocarcinoma progression. Cancer Sci. 115, 2673–2685 (2024).
Google Scholar
Wang, R. et al. H3K9 lactylation in malignant cells facilitates CD8+ T cell dysfunction and poor immunotherapy response. Cell Rep. 43, 114686 (2024).
Google Scholar
Zhang, H. R. et al. The GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment in pancreatic cancer. Cell Death Dis. 15, 244 (2024).
Google Scholar
Chen, J. et al. Lactylated apolipoprotein C-II induces immunotherapy resistance by promoting extracellular lipolysis. Adv. Sci. 11, e2406333 (2024).
Google Scholar
Xu, D. et al. The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis. Nature 580, 530–535 (2020).
Google Scholar
Shao, F. et al. Association of phosphoenolpyruvate carboxykinase 1 protein kinase activity-dependent sterol regulatory element-binding protein 1 activation with prognosis of oesophageal carcinoma. Eur. J. Cancer 142, 123–131 (2021).
Google Scholar
Wang, X. et al. PIN1 prolyl isomerase promotes initiation and progression of bladder cancer through the SREBP2-mediated cholesterol biosynthesis pathway. Cancer Discov. 15, 633–655 (2025).
Google Scholar
Tan, W. et al. Posttranscriptional regulation of de novo lipogenesis by glucose-induced O-GlcNAcylation. Mol. Cell 81, 1890–1904.e7 (2021).
Google Scholar
Lee, G. et al. Post-transcriptional regulation of de novo lipogenesis by mTORC1-S6K1-SRPK2 signaling. Cell 171, 1545–1558.e18 (2017).
Google Scholar
He, X. et al. PI3Kβ functions as a protein kinase to promote cellular protein O-GlcNAcylation and acetyl-CoA production for tumor growth. Mol. Cell 85, 1411–1425.e8 (2025).
Google Scholar
Liu, J. et al. O-GlcNAcylation of ATP-citrate lyase couples glucose supply to lipogenesis for rapid tumor cell proliferation. Proc. Natl. Acad. Sci. USA 121, e2402674121 (2024).
Google Scholar
Xu, Y. et al. USP11 promotes lipogenesis and tumorigenesis by regulating SREBF1 stability in hepatocellular carcinoma. Cell Commun. Signal. 22, 550 (2024).
Google Scholar
Chen, X. et al. TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability. J. Exp. Clin. Cancer Res. 42, 34 (2023).
Google Scholar
Noh, K. H. et al. Ubiquitination of PPAR-gamma by pVHL inhibits ACLY expression and lipid metabolism, is implicated in tumor progression. Metabolism 110, 154302 (2020).
Google Scholar
Ning, Z. et al. USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma. Nat. Commun. 13, 2187 (2022).
Google Scholar
Hu, Y. et al. Fatty Acid Synthase-Suppressor Screening Identifies Sorting Nexin 8 as a Therapeutic Target for NAFLD. Hepatology 74, 2508–2525 (2021).
Google Scholar
Mo, Y. et al. ZDHHC20 mediated S-palmitoylation of fatty acid synthase (FASN) promotes hepatocarcinogenesis. Mol. Cancer 23, 274 (2024).
Google Scholar
Liu, B. et al. Targeting ZDHHC21/FASN axis for the treatment of diffuse large B-cell lymphoma. Leukemia 38, 351–364 (2024).
Google Scholar
Liu, Z. et al. Deficiency of SIAH1 promotes the formation of filopodia by increasing the accumulation of FASN in liver cancer. Cell Death Dis. 15, 537 (2024).
Google Scholar
Zhou, S. et al. eIF3f promotes tumour malignancy by remodelling fatty acid biosynthesis in hepatocellular carcinoma. J. Hepatol. 83, 712–728 (2025).
Google Scholar
Xie, P. et al. Neddylation of PTEN regulates its nuclear import and promotes tumor development. Cell Res. 31, 291–311 (2021).
Google Scholar
Zhang, Z. et al. DHHC9-mediated GLUT1 S-palmitoylation promotes glioblastoma glycolysis and tumorigenesis. Nat. Commun. 12, 5872 (2021).
Google Scholar
Meng, Y. et al. Glycolytic enzyme PFKL governs lipolysis by promoting lipid droplet-mitochondria tethering to enhance β-oxidation and tumor cell proliferation. Nat. Metab. 6, 1092–1107 (2024).
Google Scholar
Liu, F. et al. PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability. EMBO J. 40, e108065 (2021).
Google Scholar
Zeng, Y. et al. TRAF3 loss protects glioblastoma cells from lipid peroxidation and immune elimination via dysregulated lipid metabolism. J. Clin. Investig. 135, (2025).
Shan, J. et al. Palmitoyltransferase ZDHHC6 promotes colon tumorigenesis by targeting PPARγ-driven lipid biosynthesis via regulating lipidome metabolic reprogramming. J. Exp. Clin. Cancer Res. 43, 227 (2024).
Google Scholar
Qian, X. et al. Transferrin promotes fatty acid oxidation and liver tumor growth through PHD2-mediated PPARα hydroxylation in an iron-dependent manner. Proc. Natl. Acad. Sci. USA 122, e2412473122 (2025).
Google Scholar
Yang, M. et al. S100P is a ferroptosis suppressor to facilitate hepatocellular carcinoma development by rewiring lipid metabolism. Nat. Commun. 16, 509 (2025).
Google Scholar
Gayle, S. et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood 129, 1768–1778 (2017).
Google Scholar
de Campos, C. B. et al. Identification of PIKfyve kinase as a target in multiple myeloma. Haematologica 105, 1641–1649 (2020).
Google Scholar
Cheng, C. et al. Targeting PIKfyve-driven lipid metabolism in pancreatic cancer. Nature 642, 776–784 (2025).
Google Scholar
Wang, Z. et al. Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. Nat. Cell Biol. 24, 1655–1665 (2022).
Google Scholar
Nguyen, T. et al. Author Correction: histone H2A Lys130 acetylation epigenetically regulates androgen production in prostate cancer. Nat. Commun. 14, 6022 (2023).
Google Scholar
Jiang, C. et al. Targeting c-Jun inhibits fatty acid oxidation to overcome tamoxifen resistance in estrogen receptor-positive breast cancer. Cell Death Dis. 14, 653 (2023).
Google Scholar
Yuan, L. et al. Fatty acid oxidation supports lymph node metastasis of cervical cancer via acetyl-CoA-mediated stemness. Adv. Sci. 11, e2308422 (2024).
Google Scholar
Jeong, D. W. et al. Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma. Nat. Commun. 14, 6370 (2023).
Google Scholar
Liu, J. et al. Lipogenic enzyme FASN promotes mutant p53 accumulation and gain-of-function through palmitoylation. Nat. Commun. 16, 1762 (2025).
Google Scholar
Peng, F. et al. Oncogenic fatty acid oxidation senses circadian disruption in sleep-deficiency-enhanced tumorigenesis. Cell Metab. 36, 1598–1618.e11 (2024).
Google Scholar
Park, M. H., Cooper, H. L. & Folk, J. E. Identification of hypusine, an unusual amino acid, in a protein from human lymphocytes and of spermidine as its biosynthetic precursor. Proc. Natl. Acad. Sci. USA 78, 2869–2873 (1981).
Google Scholar
Park, M. H. & Wolff, E. C. Hypusine, a polyamine-derived amino acid critical for eukaryotic translation. J. Biol. Chem. 293, 18710–18718 (2018).
Google Scholar
Lesurtel, M. & Clavien, P. A. Platelet-derived serotonin: translational implications for liver regeneration. Hepatology 60, 30 (2014).
Google Scholar
Gershon, M. D. & Tack, J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 132, 397–414 (2007).
Google Scholar
Wang, K. et al. PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma. Nat. Commun. 14, 1011 (2023).
Google Scholar
Han, T. et al. Phosphorylation of glutaminase by PKCε is essential for its enzymatic activity and critically contributes to tumorigenesis. Cell Res. 28, 655–669 (2018).
Google Scholar
Li, M. et al. Non-oncogene addiction to SIRT3 plays a critical role in lymphomagenesis. Cancer Cell 35, 916–931.e9 (2019).
Google Scholar
Wang, Y. Q. et al. Sirtuin5 contributes to colorectal carcinogenesis by enhancing glutaminolysis in a deglutarylation-dependent manner. Nat. Commun. 9, 545 (2018).
Google Scholar
Chen, L. et al. RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis. Signal Transduct. Target. Ther. 8, 159 (2023).
Google Scholar
Luo, L. et al. FBXO7 ubiquitinates PRMT1 to suppress serine synthesis and tumor growth in hepatocellular carcinoma. Nat. Commun. 15, 4790 (2024).
Google Scholar
Yamamoto, T. et al. PRMT1 sustains de novo fatty acid synthesis by methylating PHGDH to drive chemoresistance in triple-negative breast cancer. Cancer Res. 84, 1065–1083 (2024).
Google Scholar
Doglioni, G. et al. Aspartate signalling drives lung metastasis via alternative translation. Nature 638, 244–250 (2025).
Google Scholar
Nengroo, M. A. et al. Accumulation of succinate suppresses de novo purine synthesis through succinylation-mediated control of the mitochondrial folate cycle. Mol. Cell 85, 4215–4228.e9 (2025).
Google Scholar
Zhu, Q. et al. O-GlcNAcylation promotes pancreatic tumor growth by regulating malate dehydrogenase 1. Nat. Chem. Biol. 18, 1087–1095 (2022).
Google Scholar
Hu, T. et al. Metabolic rewiring by loss of Sirt5 promotes Kras-induced pancreatic cancer progression. Gastroenterology 161, 1584–1600 (2021).
Google Scholar
Tong, Y. et al. SUCLA2-coupled regulation of GLS succinylation and activity counteracts oxidative stress in tumor cells. Mol. Cell 81, 2303–2316.e8 (2021).
Google Scholar
Lao, Y. et al. Glutaryl-CoA dehydrogenase suppresses tumor progression and shapes an anti-tumor microenvironment in hepatocellular carcinoma. J. Hepatol. 81, 847–861 (2024).
Google Scholar
Verma, S. et al. NRF2 mediates melanoma addiction to GCDH by modulating apoptotic signalling. Nat. Cell Biol. 24, 1422–1432 (2022).
Google Scholar
Lu, Y. et al. Lactylation-Driven IGF2BP3-Mediated Serine Metabolism Reprogramming and RNA m6A-modification promotes lenvatinib resistance in HCC. Adv. Sci. 11, e2401399 (2024).
Google Scholar
Zheng, C. et al. ACAT1-mediated ME2 acetylation drives chemoresistance in ovarian cancer by linking glutaminolysis to lactate production. Adv. Sci. 12, e2416467 (2025).
Google Scholar
Yang, C. et al. Methionine orchestrates the metabolism vulnerability in cisplatin resistant bladder cancer microenvironment. Cell Death Dis. 14, 525 (2023).
Google Scholar
Wang, Y. et al. AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis. Nat. Commun. 13, 7215 (2022).
Google Scholar
Wang, N. et al. Pyruvate metabolism enzyme DLAT promotes tumorigenesis by suppressing leucine catabolism. Cell Metab. 37, 1381–1399.e1389 (2025).
Google Scholar
Nakanishi, S. et al. The polyamine-hypusine circuit controls an oncogenic translational program essential for malignant conversion in MYC-driven lymphoma. Blood Cancer Discov. 4, 294–317 (2023).
Google Scholar
Coni, S. et al. Combined inhibition of polyamine metabolism and eIF5A hypusination suppresses colorectal cancer growth through a converging effect on MYC translation. Cancer Lett. 559, 216120 (2023).
Google Scholar
Coni, S. et al. Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation. Cell Death Dis. 11, 1045 (2020).
Google Scholar
Li, H. et al. YAP/TAZ drives cell proliferation and tumor growth via a polyamine-eIF5A hypusination-LSD1 axis. Nat. Cell Biol. 24, 373–383 (2022).
Google Scholar
Shao, J. et al. Cytosolic GDH1 degradation restricts protein synthesis to sustain tumor cell survival following amino acid deprivation. EMBO J. 40, e107480 (2021).
Google Scholar
Yang, R. et al. Glutamate dehydrogenase 1-catalytic glutaminolysis feedback activates EGFR/PI3K/AKT pathway and reprograms glioblastoma metabolism. Neuro-Oncol. 27, 668–681 (2024).
Google Scholar
Yang, R. et al. Homeobox A3 and KDM6A cooperate in transcriptional control of aerobic glycolysis and glioblastoma progression. Neuro-Oncol. 25, 635–647 (2023).
Google Scholar
Zhang, T. et al. Branched-chain amino acid transaminase 1 confers EGFR-TKI resistance through epigenetic glycolytic activation. Signal Transduct. Target. Ther. 9, 216 (2024).
Google Scholar
Hu, K. et al. Glutamate dehydrogenase1 supports HIF-1α stability to promote colorectal tumorigenesis under hypoxia. EMBO J. 42, e112675 (2023).
Google Scholar
Zhao, J. et al. Structural insights into the recognition of histone H3Q5 serotonylation by WDR5. Sci. Adv. 7, eabf4291 (2021).
Google Scholar
Dong, R. et al. TGM2-mediated histone serotonylation promotes HCC progression via MYC signalling pathway. J. Hepatol. 83, 105–118 (2025).
Google Scholar
Chen, H. C. et al. Histone serotonylation regulates ependymoma tumorigenesis. Nature 632, 903–910 (2024).
Google Scholar
Zhao, S. et al. Histone H3Q5 serotonylation stabilizes H3K4 methylation and potentiates its readout. Proc. Natl. Acad. Sci. USA 118, e2016742118 (2021).
Google Scholar
Farrelly, L. A. et al. Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3. Nature 567, 535–539 (2019).
Google Scholar
Chen, X. et al. The Moonlighting function of glutaminase 2 promotes immune evasion of pancreatic ductal adenocarcinoma by tubulin tyrosine ligase-like 1-mediated Yes1 associated transcriptional regulator glutamylation. Gastroenterology 168, 1137–1152 (2025).
Google Scholar
Wei, W. et al. Asparagine drives immune evasion in bladder cancer via RIG-I stability and type I IFN signaling. J. Clin. Investig. 135, e186648 (2025).
Google Scholar
Schneider, M. A. et al. Attenuation of peripheral serotonin inhibits tumor growth and enhances immune checkpoint blockade therapy in murine tumor models. Sci. Transl. Med. 13, eabc8188 (2021).
Google Scholar
Yu, H., Qu, T., Yang, J. & Dai, Q. Serotonin acts through YAP to promote cell proliferation: mechanism and implication in colorectal cancer progression. Cell Commun. Signal. 21, 75 (2023).
Google Scholar
Ye, D. et al. Targeting SERT promotes tryptophan metabolism: mechanisms and implications in colon cancer treatment. J. Exp. Clin. Cancer Res. 40, 173 (2021).
Google Scholar
Park, B. S. et al. Polyamine and EIF5A hypusination downstream of c-Myc confers targeted therapy resistance in BRAF mutant melanoma. Mol. Cancer 23, 136 (2024).
Google Scholar
Schneider, J. L. et al. GUK1 activation is a metabolic liability in lung cancer. Cell 188, 1248–1264.e23 (2025).
Google Scholar
Tao, J. et al. ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth. Nat. Struct. Mol. Biol. 32, 853–863 (2025).
Google Scholar
Liu, T. et al. Nucleus-exported CLOCK acetylates PRPS to promote de novo nucleotide synthesis and liver tumour growth. Nat. Cell Biol. 25, 273–284 (2023).
Google Scholar
Qin, W. et al. PCK1 inhibits cGAS-STING activation by consumption of GTP to promote tumor immune evasion. J. Exp. Med. 222, e20240902 (2025).
Google Scholar
Duan, Y. et al. ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion. Nat. Cell Biol. 27, 668–682 (2025).
Google Scholar
Zhang, S. et al. PRMT1-mediated methylation of ME2 promotes hepatocellular carcinoma growth by inhibiting ubiquitination. Cell Death Dis. 15, 814 (2024).
Google Scholar
Liu, L. et al. Arginine and lysine methylation of MRPS23 promotes breast cancer metastasis through regulating OXPHOS. Oncogene 40, 3548–3563 (2021).
Google Scholar
Shao, X. et al. The palmitoyltransferase ZDHHC21 regulates oxidative phosphorylation to induce differentiation block and stemness in AML. Blood 142, 365–381 (2023).
Google Scholar
Hsu, W. J. et al. Arginine methylation of DDX3 by PRMT1 mediates mitochondrial homeostasis to promote breast cancer metastasis. Cancer Res. 84, 3023–3043 (2024).
Google Scholar
Yan, W. et al. SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression. EMBO J. 43, 2337–2367 (2024).
Google Scholar
Qian, X. et al. KDM3A senses oxygen availability to regulate PGC-1α-mediated mitochondrial biogenesis. Mol. Cell 76, 885–895.e7 (2019).
Google Scholar
Pei, X. et al. Palmitoylation of MDH2 by ZDHHC18 activates mitochondrial respiration and accelerates ovarian cancer growth. Sci. China Life Sci. 65, 2017–2030 (2022).
Google Scholar
Teng, P. et al. SIRT5-mediated ME2 desuccinylation promotes cancer growth by enhancing mitochondrial respiration. Cell Death Differ. 31, 65–77 (2024).
Google Scholar
Ma, W. et al. OXCT1 functions as a succinyltransferase, contributing to hepatocellular carcinoma via succinylating LACTB. Mol. Cell 84, 538–551.e7 (2024).
Google Scholar
Guo, D. et al. OXCT1 succinylation and activation by SUCLA2 promotes ketolysis and liver tumor growth. Mol. Cell 85, 843–856.e6 (2025).
Google Scholar
Huang, S. Y. et al. PJA1-mediated suppression of pyroptosis as a driver of docetaxel resistance in nasopharyngeal carcinoma. Nat. Commun. 15, 5300 (2024).
Google Scholar
Sun, W., Jia, M., Feng, Y. & Cheng, X. Lactate is a bridge linking glycolysis and autophagy through lactylation. Autophagy 19, 3240–3241 (2023).
Google Scholar
Li, W. et al. Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer. Autophagy 20, 114–130 (2024).
Google Scholar
Xu, Y. et al. Deacetylation of ATG7 drives the induction of macroautophagy and LC3-associated microautophagy. Autophagy 20, 1134–1146 (2024).
Google Scholar
Yang, J. et al. Inhibition of ACSS2 triggers glycolysis inhibition and nuclear translocation to activate SIRT1/ATG5/ATG2B deacetylation axis, promoting autophagy and reducing malignancy and chemoresistance in ovarian cancer. Metabolism 162, 156041 (2025).
Google Scholar
Rowland, L. A. & Czech, M. P. Fatty acid availability controls autophagy and associated cell functions. Autophagy 19, 3242–3243 (2023).
Google Scholar
Wang, S. et al. VCP enhances autophagy-related osteosarcoma progression by recruiting USP2 to inhibit ubiquitination and degradation of FASN. Cell Death Dis. 15, 788 (2024).
Google Scholar
Wei, F. et al. ZDHHC7-mediated S-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation. Autophagy 20, 2719–2737 (2024).
Google Scholar
Chen, L. et al. USP13 facilitates a ferroptosis-to-autophagy switch by activation of the NFE2L2/NRF2-SQSTM1/p62-KEAP1 axis dependent on the KRAS signaling pathway. Autophagy 21, 565–582 (2025).
Google Scholar
Wang, L. et al. ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation. Nat. Chem. Biol. 21, 894–905 (2025).
Google Scholar
Li, L. et al. WNK1 interaction with KEAP1 promotes NRF2 stabilization to enhance the oxidative stress response in hepatocellular carcinoma. Cancer Res. 84, 2776–2791 (2024).
Google Scholar
Tian, L. et al. aPKCι promotes gallbladder cancer tumorigenesis and gemcitabine resistance by competing with Nrf2 for binding to Keap1. Redox Biol. 22, 101149 (2019).
Google Scholar
Wang, X. et al. DDRGK1 enhances osteosarcoma chemoresistance via inhibiting KEAP1-mediated NRF2 ubiquitination. Adv. Sci. 10, e2204438 (2023).
Google Scholar
Wei, J. et al. TRIM25 promotes temozolomide resistance in glioma by regulating oxidative stress and ferroptotic cell death via the ubiquitination of keap1. Oncogene 42, 2103–2112 (2023).
Google Scholar
Liu, Y. et al. TRIM25 promotes the cell survival and growth of hepatocellular carcinoma through targeting Keap1-Nrf2 pathway. Nat. Commun. 11, 348 (2020).
Google Scholar
Liu, W. et al. TRIM22 inhibits osteosarcoma progression through destabilizing NRF2 and thus activation of ROS/AMPK/mTOR/autophagy signaling. Redox Biol. 53, 102344 (2022).
Google Scholar
Sun, Q. et al. Loss of xanthine oxidoreductase potentiates propagation of hepatocellular carcinoma stem cells. Hepatology 71, 2033–2049 (2020).
Google Scholar
Choi, E. J. et al. Metabolic stress induces a double-positive feedback loop between AMPK and SQSTM1/p62 conferring dual activation of AMPK and NFE2L2/NRF2 to synergize antioxidant defense. Autophagy 20, 2490–2510 (2024).
Google Scholar
Li, D. et al. CST1 inhibits ferroptosis and promotes gastric cancer metastasis by regulating GPX4 protein stability via OTUB1. Oncogene 42, 83–98 (2023).
Google Scholar
Fan, Y. et al. PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer. Nat. Cell Biol. 27, 641–653 (2025).
Google Scholar
Huang, B. et al. Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis. Nat. Commun. 16, 867 (2025).
Google Scholar
Zhou, L. et al. Palmitoylation of GPX4 via the targetable ZDHHC8 determines ferroptosis sensitivity and antitumor immunity. Nat. Cancer 6, 768–785 (2025).
Google Scholar
Yang, Z. et al. Lactylation of HDAC1 confers resistance to ferroptosis in colorectal cancer. Adv. Sci. 12, e2408845 (2025).
Google Scholar
Yang, J. S. et al. ALDH7A1 protects against ferroptosis by generating membrane NADH and regulating FSP1. Cell 188, 2569–2585.e20 (2025).
Google Scholar
Han, Y. et al. IL-1β-associated NNT acetylation orchestrates iron-sulfur cluster maintenance and cancer immunotherapy resistance. Mol. Cell 83, 1887–1902.e8 (2023).
Google Scholar
Niu, K. et al. NSUN2 lactylation drives cancer cell resistance to ferroptosis through enhancing GCLC-dependent glutathione synthesis. Redox Biol. 79, 103479 (2025).
Google Scholar
Liu, T., Jiang, L., Tavana, O. & Gu, W. The deubiquitylase OTUB1 mediates ferroptosis via stabilization of SLC7A11. Cancer Res. 79, 1913–1924 (2019).
Google Scholar
Liu, X. et al. The deubiquitinase OTUD5 stabilizes SLC7A11 to promote progression and reduce paclitaxel sensitivity in triple-negative breast cancer. Cancer Lett. 604, 217232 (2024).
Google Scholar
Wang, Z. et al. TRIM3 facilitates ferroptosis in non-small cell lung cancer through promoting SLC7A11/xCT K11-linked ubiquitination and degradation. Cell Death Differ. 31, 53–64 (2024).
Google Scholar
Chen, Q. et al. SOCS2-enhanced ubiquitination of SLC7A11 promotes ferroptosis and radiosensitization in hepatocellular carcinoma. Cell Death Differ. 30, 137–151 (2023).
Google Scholar
Tang, J. et al. Targeting USP8 inhibits O-GlcNAcylation of SLC7A11 to promote ferroptosis of hepatocellular carcinoma via stabilization of OGT. Adv. Sci. 10, 2302953 (2023).
Google Scholar
Zhang, H. et al. A ROS-mediated oxidation-O-GlcNAcylation cascade governs ferroptosis. Nat. Cell Biol. 27, 1288–1300 (2025).
Google Scholar
Cui, Z. et al. TRIM21/USP15 balances ACSL4 stability and the imatinib resistance of gastrointestinal stromal tumors. Br. J. Cancer 130, 526–541 (2024).
Google Scholar
Shan, G. et al. Ferroptosis-induced SUMO2 lactylation counteracts ferroptosis by enhancing ACSL4 degradation in lung adenocarcinoma. Cell Discov. 11, 81 (2025).
Google Scholar
Ding, Y. et al. Disruption of the sorcin‒PAX5 protein‒protein interaction induces ferroptosis by promoting the FBXL12-mediated ubiquitination of ALDH1A1 in pancreatic cancer. J. Hematol. Oncol. 18, 27 (2025).
Google Scholar
Zhang, W. et al. SMURF2 predisposes cancer cell toward ferroptosis in GPX4-independent manners by promoting GSTP1 degradation. Mol. Cell 83, 4352–4369.e8 (2023).
Google Scholar
Can, C. et al. Exosomal circ_0006896 promotes AML progression via interaction with HDAC1 and restriction of antitumor immunity. Mol. Cancer 24, 4 (2025).
Google Scholar
Zhou, X. et al. O-GlcNAcylation regulates the stability of transferrin receptor (TFRC) to control the ferroptosis in hepatocellular carcinoma cells. Redox Biol. 73, 103182 (2024).
Google Scholar
Liu, Z. et al. E3 ubiquitin ligase DTX2 fosters ferroptosis resistance via suppressing NCOA4-mediated ferritinophagy in non-small cell lung cancer. Drug Resist. Updat. 77, 101154 (2024).
Google Scholar
Mansuer, M., Zhou, L., Wang, C., Gao, L. & Jiang, Y. Erianin induces ferroptosis in GSCs via REST/LRSAM1 mediated SLC40A1 ubiquitination to overcome TMZ resistance. Cell Death Dis. 15, 522 (2024).
Google Scholar
Tsvetkov, P. et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science 375, 1254–1261 (2022).
Google Scholar
Sun, L. et al. Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer. Nat. Commun. 14, 6523 (2023).
Google Scholar
Yang, Z. et al. Hypoxia inducible factor-1α drives cancer resistance to cuproptosis. Cancer Cell 43, 937–954.e9 (2025).
Google Scholar
Cui, Z. et al. MYO1F regulates T-cell activation and glycolytic metabolism by promoting the acetylation of GAPDH. Cell. Mol. Immunol. 22, 176–190 (2025).
Google Scholar
Wang, X. et al. A GAPDH serotonylation system couples CD8+ T cell glycolytic metabolism to antitumor immunity. Mol. Cell 84, 760–775.e7 (2024).
Google Scholar
Sun, F. et al. SUMOylation of PDPK1 is required to maintain glycolysis-dependent CD4 T-cell homeostasis. Cell Death Dis. 13, 181 (2022).
Google Scholar
Chowdhury, S. et al. Intracellular Acetyl CoA potentiates the therapeutic efficacy of antitumor CD8+ T cells. Cancer Res. 82, 2640–2655 (2022).
Google Scholar
Kaymak, I. et al. ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses. J. Exp. Med. 221, e20231820 (2024).
Google Scholar
Wu, Z. et al. SENP7 senses oxidative stress to sustain metabolic fitness and antitumor functions of CD8+ T cells. J. Clin. Investig. 132, e155224 (2022).
Google Scholar
He, J. et al. Autocrine VEGF-B signaling maintains lipid synthesis and mitochondrial fitness to support T cell immune responses. J. Clin. Investig. 134, e176586 (2024).
Google Scholar
Ma, R. et al. A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8+ T cells. Nat. Cell Biol. 20, 21–27 (2018).
Google Scholar
Zhang, H. et al. Ketogenesis-generated β-hydroxybutyrate is an epigenetic regulator of CD8+ T-cell memory development. Nat. Cell Biol. 22, 18–25 (2020).
Google Scholar
Raychaudhuri, D. et al. Histone lactylation drives CD8+ T cell metabolism and function. Nat. Immunol. 25, 2140–2151 (2024).
Google Scholar
He, J. et al. Glucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development. Nat. Commun. 12, 4371 (2021).
Google Scholar
Wang, T. et al. SENP1-Sirt3 signaling controls mitochondrial protein acetylation and metabolism. Mol. Cell 75, 823–834.e5 (2019).
Google Scholar
Qiu, Y. et al. Mannose metabolism reshapes T cell differentiation to enhance anti-tumor immunity. Cancer Cell 43, 103–121.e8 (2025).
Google Scholar
Ma, S. et al. Nutrient-driven histone code determines exhausted CD8+ T cell fates. Science 387, eadj3020 (2025).
Google Scholar
Wang, F. et al. ZFP91 disturbs metabolic fitness and antitumor activity of tumor-infiltrating T cells. J. Clin. Investig. 131, e144318 (2021).
Google Scholar
Wang, J. et al. CBX4 suppresses CD8+ T cell antitumor immunity by reprogramming glycolytic metabolism. Theranostics 14, 3793–3809 (2024).
Google Scholar
Minogue, E. et al. Glutarate regulates T cell metabolism and anti-tumour immunity. Nat. Metab. 5, 1747–1764 (2023).
Google Scholar
Hu, Z. et al. SIRT7 regulates T-cell antitumor immunity through modulation BCAA and fatty acid metabolism. Cell Death Differ. 32, 1777–1790 (2025).
Google Scholar
Zhang, Z. et al. Palmitoylation of TIM-3 promotes immune exhaustion and restrains antitumor immunity. Sci. Immunol. 9, eadp7302 (2024).
Google Scholar
Song, M. et al. IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity. Nature 562, 423–428 (2018).
Google Scholar
Bian, Y. et al. Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. Nature 585, 277–282 (2020).
Google Scholar
Xiao, J. et al. Uridine depletion impairs CD8+ T cell antitumor activity through N-glycosylation. Cell Metab. 38, 616–632.e8 (2026).
Google Scholar
Bingol, B. et al. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature 510, 370–375 (2014).
Google Scholar
Ikeda, H. et al. Immune evasion through mitochondrial transfer in the tumour microenvironment. Nature 638, 225–236 (2025).
Google Scholar
Zhou, C. et al. Mutant KRAS-activated circATXN7 fosters tumor immunoescape by sensitizing tumor-specific T cells to activation-induced cell death. Nat. Commun. 15, 499 (2024).
Google Scholar
Xiong, J. et al. Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol. Cell 82, 1660–1677.e10 (2022).
Google Scholar
Zhou, X. et al. Increases in 4-acetaminobutyric acid generated by phosphomevalonate kinase suppress CD8+ T cell activation and allow tumor immune escape. Adv. Sci. 11, e2403629 (2024).
Google Scholar
Li, G., Wen, Z. & Xiong, S. Microenvironmental β-TrCP negates amino acid transport to trigger CD8+ T cell exhaustion in human non-small cell lung cancer. Cell Rep. 44, 115128 (2025).
Google Scholar
Hu, C. et al. Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8+T cells. Cell Metab. 36, 630–647.e8 (2024).
Google Scholar
Zhou, X. et al. Inhibition of DUSP18 impairs cholesterol biosynthesis and promotes anti-tumor immunity in colorectal cancer. Nat. Commun. 15, 5851 (2024).
Google Scholar
Liang, J. et al. Riplet promotes lipid metabolism changes associated with CD8 T cell exhaustion and anti-PD-1 resistance in hepatocellular carcinoma. Sci. Immunol. 10, eado3485 (2025).
Google Scholar
Lin, J. et al. SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma. J. Exp. Clin. Cancer Res.42, 339 (2023).
Google Scholar
Kim, D. H. et al. Glutamine-derived aspartate is required for eIF5A hypusination-mediated translation of HIF-1α to induce the polarization of tumor-associated macrophages. Exp. Mol. Med. 56, 1123–1136 (2024).
Google Scholar
De Leo, A. et al. Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma. Immunity 57, 1105–1123.e8 (2024).
Google Scholar
Ugolini, A. et al. Functional reprogramming of neutrophils within the brain tumor microenvironment by hypoxia-driven histone lactylation. Cancer Discov. 15, 1270–1296 (2025).
Google Scholar
Cai, J. et al. Targeting SRSF10 might inhibit M2 macrophage polarization and potentiate anti-PD-1 therapy in hepatocellular carcinoma. Cancer Commun. 44, 1231–1260 (2024).
Google Scholar
Zhang, N. et al. Cholangiocarcinoma PDHA1 succinylation suppresses macrophage antigen presentation via alpha-ketoglutaric acid accumulation. Nat. Commun. 16, 3177 (2025).
Google Scholar
Zhu, C. X. et al. Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma. J. Hepatol. 81, 690–703 (2024).
Google Scholar
Wei, X. et al. Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway. J. Immunother. Cancer 13, e009993 (2025).
Google Scholar
Yu, S. et al. Tumor-associated macrophage-induced circMRCKα encodes a peptide to promote glycolysis and progression in hepatocellular carcinoma. Cancer Lett. 591, 216872 (2024).
Google Scholar
Lan, T. et al. The protein circPETH-147aa regulates metabolic reprogramming in hepatocellular carcinoma cells to remodel immunosuppressive microenvironment. Nat. Commun. 16, 333 (2025).
Google Scholar
Wang, Y. et al. M2 tumor-associated macrophages-derived exosomal MALAT1 promotes glycolysis and gastric cancer progression. Adv. Sci. 11, e2309298 (2024).
Google Scholar
Ma, L. et al. Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer. Signal Transduct. Target. Ther. 9, 64 (2024).
Google Scholar
Fan, Y. et al. Itaconate transporter SLC13A3 confers immunotherapy resistance via alkylation-mediated stabilization of PD-L1. Cell Metab. 37, 514–526.e5 (2025).
Google Scholar
Wang, S. et al. Lactate reprograms glioblastoma immunity through CBX3-regulated histone lactylation. J. Clin. Investig. 134, e176851 (2024).
Google Scholar
Lu, S. et al. Succinate-loaded tumor cell-derived microparticles reprogram tumor-associated macrophage metabolism. Sci. Transl. Med. 17, eadr4458 (2025).
Google Scholar
Wang, A. et al. USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis. J. Clin. Investig. 133, e169365 (2023).
Google Scholar
Wang, A. et al. ZFP91 is required for the maintenance of regulatory T cell homeostasis and function. J. Exp. Med. 218, e20201217 (2021).
Google Scholar
Sharma, A. et al. Glut3 promotes cellular O-GlcNAcylation as a distinctive tumor-supportive feature in Treg cells. Cell. Mol. Immunol. 21, 1474–1490 (2024).
Google Scholar
Zhang, G. et al. CPT1A induction following epigenetic perturbation promotes MAVS palmitoylation and activation to potentiate antitumor immunity. Mol. Cell 83, 4370–4385.e9 (2023).
Google Scholar
Lu, X. et al. NAD+ metabolism reprogramming drives SIRT1-dependent deacetylation inducing PD-L1 nuclear localization in cervical cancer. Adv. Sci. 12, e2412109 (2025).
Google Scholar
Yang, G. et al. Succinylation of tumor suppressor PPP2R1A K541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling to display oncogene function. Acta Pharm. Sin. B 15, 5294–5311 (2025).
Google Scholar
Sun, S. et al. Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed α-tubulin lactylation. Nat. Commun. 15, 8377 (2024).
Google Scholar
Chu, T. et al. Metabolism archetype cancer cells induce protumor TREM2+ macrophages via oxLDL-mediated metabolic interplay in hepatocellular carcinoma. Nat. Commun. 16, 6770 (2025).
Google Scholar
Zhao, H. et al. Single-cell analysis of posttranslational modifications identifies immunosuppressive macrophage subtypes in the HBV-positive hepatocellular carcinoma microenvironment. Cancer Immunol. Res. 13, 1303–1317 (2025).
Google Scholar
Wang, Y. et al. O-GlcNAcylation destabilizes the active tetrameric PKM2 to promote the Warburg effect. Proc. Natl. Acad. Sci. USA 114, 13732–13737 (2017).
Google Scholar
Singh, J. P. et al. O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth. Oncogene 39, 560–573 (2020).
Google Scholar
Wang, X. et al. Histone lactylation dynamics: unlocking the triad of metabolism, epigenetics, and immune regulation in metastatic cascade of pancreatic cancer. Cancer Lett. 598, 217117 (2024).
Google Scholar
Qin, T. et al. Nuclear to cytoplasmic transport is a druggable dependency in HDAC7-driven small cell lung cancer. Adv. Sci. 12, e2413445 (2025).
Google Scholar
Zhang, P. et al. Novel post-translational modification learning signature reveals B4GALT2 as an immune exclusion regulator in lung adenocarcinoma. J. Immunother. Cancer 13, e010787 (2025).
Google Scholar
Jutzi, J. S. et al. Whole-genome CRISPR screening identifies N-glycosylation as a genetic and therapeutic vulnerability in CALR-mutant MPNs. Blood 140, 1291–1304 (2022).
Google Scholar
Li, L., Li, W., Xiao, L. & Lai, W. Lactylation signature identifies liver fibrosis phenotypes and traces fibrotic progression to hepatocellular carcinoma. Front. Immunol. 15, 1433393 (2024).
Google Scholar
Jabbour, E. et al. Ponatinib vs imatinib in frontline Philadelphia chromosome-positive acute lymphoblastic leukemia: a randomized clinical trial. JAMA 331, 1814–1823 (2024).
Google Scholar
Cho, B. C. et al. Osimertinib versus standard of care EGFR TKI as first-line treatment in patients with EGFRm advanced NSCLC: FLAURA asian subset. J. Thorac. Oncol. 14, 99–106 (2019).
Google Scholar
Ramalingam, S. S. et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N. Engl. J. Med. 382, 41–50 (2020).
Google Scholar
Pietrantonio, F. et al. Overall survival analysis of the phase III CodeBreaK 300 study of Sotorasib plus panitumumab versus investigator’s choice in chemorefractory KRAS G12C colorectal cancer. J. Clin. Oncol. 43, 2147–2154 (2025).
Google Scholar
Scholes, N. S. et al. Inhibitors supercharge kinase turnover through native proteolytic circuits. Nature 649, 1032–1041 (2026).
Google Scholar
Zhang, Y. et al. EGFR-TKIs induced DPP4 drives metabolic reprogramming of persister cells in lung cancer. Adv. Sci. 12, e06950 (2025).
Google Scholar
Stine, Z. E., Schug, Z. T., Salvino, J. M. & Dang, C. V. Targeting cancer metabolism in the era of precision oncology. Nat. Rev. Drug Discov. 21, 141–162 (2022).
Google Scholar
Gautam, J. et al. ACLY inhibition promotes tumour immunity and suppresses liver cancer. Nature 645, 507–517 (2025).
Google Scholar
Yee, A. J. et al. Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial. Lancet Oncol. 17, 1569–1578 (2016).
Google Scholar
Yang, L. et al. Preclinical and first-in-human of purinostat mesylate, a novel selective HDAC I/IIb inhibitor, in relapsed/refractory multiple myeloma and lymphoma. Signal Transduct. Target. Ther. 10, 201 (2025).
Google Scholar
Fischer, M. A. et al. Novel hydroxamic acid derivative induces apoptosis and constrains autophagy in leukemic cells. J. Adv. Res. 60, 201–214 (2024).
Google Scholar
Peng, X. et al. Deacetylation of TALDO1 by HDAC6 promotes glycolysis and nasopharyngeal carcinoma progression through a moonlighting function. Cell Death Dis. 16, 743 (2025).
Google Scholar
Pytel, W. A. et al. The allosteric regulator inositol phosphate dramatically affects the efficacy and selectivity of inhibitors for different HDAC complexes. J. Am. Chem. Soc. 147, 36044–36052 (2025).
Google Scholar
Shang, T. et al. The noncanonical function of liver-type phosphofructokinase potentiates the efficacy of HDAC inhibitors in cancer. Signal Transduct. Target. Ther. 10, 341 (2025).
Google Scholar
Li, W. et al. NADPH levels affect cellular epigenetic state by inhibiting HDAC3-Ncor complex. Nat. Metab. 3, 75–89 (2021).
Google Scholar
Zhao, T. et al. Derepressing nuclear pyruvate dehydrogenase induces therapeutic cancer cell reprogramming. Cell Metab. 37, 1667–1681.e13 (2025).
Google Scholar
Wang, M. et al. Vascular normalization augments the antitumor efficacy of combined HDAC inhibitor with immunotherapy in solid tumors. Cancer Discov. 15, 1883–1904 (2025).
Google Scholar
Mustafa, A. H. M. & Krämer, O. H. Pharmacological modulation of the crosstalk between aberrant janus kinase signaling and epigenetic modifiers of the histone deacetylase family to treat cancer. Pharmacol. Rev. 75, 35–61 (2023).
Google Scholar
Zhao, C. et al. Discovery of novel fedratinib-based HDAC/JAK/BRD4 triple inhibitors with remarkable antitumor activity against triple negative breast cancer. J. Med. Chem. 66, 14150–14174 (2023).
Google Scholar
Zeleke, T. Z. et al. Network-based assessment of HDAC6 activity predicts preclinical and clinical responses to the HDAC6 inhibitor ricolinostat in breast cancer. Nat. Cancer 4, 257–275 (2023).
Google Scholar
Jin, J. et al. Human HDAC6 senses valine abundancy to regulate DNA damage. Nature 637, 215–223 (2025).
Google Scholar
Landgren, O. et al. Carfilzomib with immunomodulatory drugs for the treatment of newly diagnosed multiple myeloma. Leukemia 33, 2127–2143 (2019).
Google Scholar
Fu, D. J. & Wang, T. Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions. J. Hematol. Oncol. 16, 87 (2023).
Google Scholar
Izutsu, K. et al. An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma. Blood 141, 1159–1168 (2023).
Google Scholar
Chen, S. et al. MTA-cooperative PRMT5 inhibitors enhance T cell-mediated antitumor activity in MTAP-loss tumors. J. Immunother. Cancer 12, e009600 (2024).
Google Scholar
Drizyte-Miller, K. et al. Combination of the MTA-cooperative PRMT5 inhibitor BMS-986504 and KRAS inhibitors is an effective treatment strategy for MTAP-deleted KRAS-mutant pancreatic cancer. Cancer Res. 85, 3540–3557 (2025).
Google Scholar
Jeong, J. et al. NSD2 inhibitors rewire chromatin to treat lung and pancreatic cancers. Nature 649, 205–215 (2026).
Google Scholar
Figarol, S. et al. Farnesyltransferase inhibition overcomes oncogene-addicted non-small cell lung cancer adaptive resistance to targeted therapies. Nat. Commun. 15, 5345 (2024).
Google Scholar
Tan, X. P. et al. Blockade of NMT1 enzymatic activity inhibits N-myristoylation of VILIP3 protein and suppresses liver cancer progression. Signal Transduct. Target. Ther. 8, 14 (2023).
Google Scholar
McHugh, D. et al. COPI vesicle formation and N-myristoylation are targetable vulnerabilities of senescent cells. Nat. Cell Biol. 25, 1804–1820 (2023).
Google Scholar
Kasahara, T. et al. Anticancer approach by targeted activation of a global inhibitor of sialyltransferases with acrolein. Chem. Sci. 15, 9566–9573 (2024).
Google Scholar
Mou, J. et al. A potent oral sialylation inhibitor augments the immunotherapy in pancreatic ductal adenocarcinoma. ACS Cent. Sci. 11, 1969–1983 (2025).
Google Scholar
Campone, M. et al. Vepdegestrant, a PROTAC estrogen receptor degrader, in advanced breast cancer. N. Engl. J. Med. 393, 556–568 (2025).
Google Scholar
Zhou, J. et al. STAT5 and STAT3 balance shapes dendritic cell function and tumour immunity. Nature 643, 519–528 (2025).
Google Scholar
Wang, Y. et al. Discovery of a bifunctional PKMYT1-targeting PROTAC empowered by AI-generation. Nat. Commun. 16, 10759 (2025).
Google Scholar
Zheng, M. et al. Rational design and synthesis of novel dual PROTACs for simultaneous degradation of EGFR and PARP. J. Med. Chem. 64, 7839–7852 (2021).
Google Scholar
Wang, Z. et al. USP28-based deubiquitinase-targeting chimeras for cancer treatment. J. Am. Chem. Soc. 147, 13754–13763 (2025).
Google Scholar
He, C. et al. Construction of small-molecule deubiquitinase-targeting chimeras to reactivate and stabilize mutant p53 Y220C in vitro and in vivo. Angew. Chem. 65, e18249 (2026).
Google Scholar
Zhang, Q. et al. Protein phosphatase 5-recruiting chimeras for accelerating apoptosis-signal-regulated kinase 1 dephosphorylation with antiproliferative activity. J. Am. Chem. Soc. 145, 1118–1128 (2023).
Google Scholar
Pergu, R. et al. PhosphorylatIon-inducing Molecules For Regulating Dynamic Cellular Processes. J. Am. Chem. Soc. 147, 25316–25324 (2025).
Google Scholar
Wang, W. W., Singha Roy, S. J. & Parker, C. G. Targeted protein acetylation through chemically induced proximity. Acc. Chem. Res. 58, 2695–2707 (2025).
Google Scholar
Ma, B. et al. Targeted protein O-GlcNAcylation using bifunctional small molecules. J. Am. Chem. Soc. 146, 9779–9789 (2024).
Google Scholar
Li, L. et al. N-deglycosylation targeting chimera (DGlyTAC): a strategy for immune checkpoint proteins inactivation by specifically removing N-glycan. Signal Transduct. Target. Ther. 10, 139 (2025).
Google Scholar
Qian, K. et al. HDAC8 enhances the function of HIF-2α by deacetylating ETS1 to decrease the sensitivity of TKIs in ccRCC. Adv. Sci. 11, e2401142 (2024).
Google Scholar
Kansy, A. G. et al. Pharmacological degradation of ATR induces antiproliferative DNA replication stress in leukemic cells. Mol. Oncol. 18, 1958–1965 (2024).
Google Scholar
Marx, C. et al. DNA damage response regulator ATR licenses PINK1-mediated mitophagy. Nucleic Acids Res. 53, gkaf178 (2025).
Google Scholar
Zeyn, Y. et al. Histone deacetylase inhibitors modulate hormesis in leukemic cells with mutant FMS-like tyrosine kinase-3. Leukemia 37, 2319–2323 (2023).
Google Scholar
Halilovic, M. et al. Selective degradation of mutant FMS-like tyrosine kinase-3 requires BIM-dependent depletion of heat shock proteins. Leukemia 38, 2561–2572 (2024).
Google Scholar
Zhu, Q. et al. Enzyme-activated sugar-coated bifunctional degraders. J. Am. Chem. Soc. 147, 34672–34680 (2025).
Google Scholar
Gao, Y. et al. GLUTs-facilitated targeting BRD4 degradation in breast cancer through carbohydrate-conjugated PROTACs. J. Med. Chem. 68, 17046–17064 (2025).
Google Scholar
Serafini, M. et al. Indolequinone-based hypoxia-activated proteolysis targeting chimeras selectively degrade BRD4 in hypoxic cancer cells. J. Am. Chem. Soc. 147, 36352–36364 (2025).
Google Scholar
Sun, C. et al. Enzyme-activated orthogonal proteolysis chimeras for tumor microenvironment-responsive immunomodulation. Angew. Chem. Int. Ed Engl. 64, e202423057 (2025).
Google Scholar
Guenette, R. G., Yang, S. W., Min, J., Pei, B. & Potts, P. R. Target and tissue selectivity of PROTAC degraders. Chem. Soc. Rev. 51, 5740–5756 (2022).
Google Scholar
Guerreiro, A. et al. Non-natural MUC1 glycopeptide homogeneous cancer vaccine with enhanced immunogenicity and therapeutic activity. Angew. Chem. Int. Ed. Engl. 63, e202411009 (2024).
Google Scholar
Wang, S. W. et al. Mechanism of antigen presentation and specificity of antibody cross-reactivity elicited by an oligosaccharide-conjugate cancer vaccine. J. Am. Chem. Soc. 145, 9840–9849 (2023).
Google Scholar
Engelhard, V. H. et al. MHC-restricted phosphopeptide antigens: preclinical validation and first-in-humans clinical trial in participants with high-risk melanoma. J. Immunother. Cancer 8, (2020).
Dao, T. et al. A TCR mimic monoclonal antibody reactive with the ‘public’ phospho-neoantigen pIRS2/HLA-A*02:01 complex. JCI Insight 7, e151624 (2022).
Google Scholar
Choudhury, R. H. et al. PAD-2-mediated citrullination of nucleophosmin provides an effective target for tumor immunotherapy. J. Immunother. Cancer 10, e003526 (2022).
Google Scholar
Cook, K. W. et al. Homocitrullination of lysine residues mediated by myeloid-derived suppressor cells in the tumor environment is a target for cancer immunotherapy. J. Immunother. Cancer 9, e001910 (2021).
Google Scholar
Brentville, V. A. et al. Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses. J. Immunother. Cancer 8, e000560 (2020).
Google Scholar
Huang, C. S. et al. Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study. J. Immunother. Cancer 8, e000342 (2020).
Google Scholar
Zhong, L. et al. Hyperacute rejection-engineered oncolytic virus for interventional clinical trial in refractory cancer patients. Cell 188, 1119–1136.e23 (2025).
Google Scholar
Zhang, Z. et al. A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy. Cancer Cell 40, 1060–1069.e7 (2022).
Google Scholar
Kaufman, B. et al. N-glycosylation of PD-L1 modulates the efficacy of immune checkpoint blockades targeting PD-L1 and PD-1. Mol. Cancer 24, 140 (2025).
Google Scholar
Song, X. et al. Pharmacologic suppression of B7-H4 glycosylation restores antitumor immunity in immune-cold breast cancers. Cancer Discov. 10, 1872–1893 (2020).
Google Scholar
Huang, Y. et al. Targeting site-specific N-glycosylated B7H3 induces potent antitumor immunity. Nat. Commun. 16, 3546 (2025).
Google Scholar
Zhou, R. W. et al. Safe immunosuppression-resistant pan-cancer immunotherapeutics by velcro-like density-dependent targeting of tumor-associated carbohydrate antigens. Cell 188, 6737–6753.e18 (2025).
Google Scholar
Zhai, Y. et al. Post-translational modified neoantigens in autoimmune diseases: challenges of immune tolerance. Adv. Sci. 12, e01766 (2025).
Google Scholar
Qin, J. et al. Ketogenic diet reshapes cancer metabolism through lysine β-hydroxybutyrylation. Nat. Metab. 6, 1505–1528 (2024).
Google Scholar
Wang, J. et al. Dietary palmitic acid drives a palmitoyltransferase ZDHHC15-YAP feedback loop promoting tumor metastasis. Adv. Sci. 12, e2409883 (2025).
Google Scholar
Nshanian, M. et al. Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression. Nat. Metab. 7, 196–211 (2025).
Google Scholar
Li, S. et al. Short-chain fatty acids and cancer. Trends Cancer 11, 154–168 (2025).
Google Scholar
Liang, L. et al. Alterations in PD-L1 succinylation shape anti-tumor immune responses in melanoma. Nat. Genet. 57, 680–693 (2025).
Google Scholar
Frisch, A. T. et al. Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior T cells for cancer immunotherapy. Cell Metab. 37, 870–885.e8 (2025).
Google Scholar
Yuan, H. et al. Lysine catabolism reprograms tumour immunity through histone crotonylation. Nature 617, 818–826 (2023).
Google Scholar
Cui, Y. H. et al. Targeting DTX2/UFD1-mediated FTO degradation to regulate antitumor immunity. Proc. Natl. Acad. Sci. USA 121, e2407910121 (2024).
Google Scholar
Tong, H. et al. Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation. Cell Metab. 36, 2493–2510.e9 (2024).
Google Scholar
Yang, H. et al. Remodelling of the translatome controls diet and its impact on tumorigenesis. Nature 633, 189–197 (2024).
Google Scholar
The UniProt Consortium UniProt: the Universal Protein Knowledgebase in 2025. Nucleic Acids Res. 53, D609–D617 (2025).
Google Scholar
Li, Z. et al. dbPTM in 2022: an updated database for exploring regulatory networks and functional associations of protein post-translational modifications. Nucleic Acids Res. 50, D471–D479 (2022).
Google Scholar
Huang, X. et al. PTMD 2.0: an updated database of disease-associated post-translational modifications. Nucleic Acids Res 53, D554–D563 (2025).
Google Scholar
Hornbeck, P. V. et al. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 43, D512–D520 (2015).
Google Scholar
Dinkel, H. et al. Phospho.ELM: a database of phosphorylation sites-update 2011. Nucleic Acids Res. 39, D261–D267 (2011).
Google Scholar
York, W. S. et al. GlyGen: computational and informatics resources for glycoscience. Glycobiology 30, 72–73 (2020).
Google Scholar
Zhang, W. et al. CPLM 4.0: an updated database with rich annotations for protein lysine modifications. Nucleic Acids Res. 50, D451–D459 (2022).
Google Scholar
Blom, N., Sicheritz-Pontén, T., Gupta, R., Gammeltoft, S. & Brunak, S. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 4, 1633–1649 (2004).
Google Scholar
Gupta, R. & Brunak, S. Prediction of glycosylation across the human proteome and the correlation to protein function. Pac. Symp. Biocomput. 310–322 (2002).
Kiemer, L., Bendtsen, J. D. & Blom, N. NetAcet: prediction of N-terminal acetylation sites. Bioinformatics 21, 1269–1270 (2005).
Google Scholar
Gou, Y. et al. GPS-SUMO 2.0: an updated online service for the prediction of SUMOylation sites and SUMO-interacting motifs. Nucleic Acids Res. 52, W238–W247 (2024).
Google Scholar
Chen, M. et al. GPS 6.0: an updated server for prediction of kinase-specific phosphorylation sites in proteins. Nucleic Acids Res. 51, W243–W250 (2023).
Google Scholar
Wang, C. et al. GPS 5.0: an update on the prediction of kinase-specific phosphorylation sites in proteins. Genomics Proteomics Bioinform. 18, 72–80 (2020).
Google Scholar
Ning, W. et al. GPS-Palm: a deep learning-based graphic presentation system for the prediction of S-palmitoylation sites in proteins. Brief. Bioinform. 22, 1836–1847 (2021).
Google Scholar
Keshava Prasad, T. S. et al. Human Protein Reference Database-2009 update. Nucleic Acids Res. 37, D767–D772 (2009).
Google Scholar
Huang, H. et al. iPTMnet: an integrated resource for protein post-translational modification network discovery. Nucleic Acids Res. 46, D542–D550 (2018).
Google Scholar

