Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63.
Google Scholar
Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: a review of the literature. Cancer. 2009;115:3379–91.
Google Scholar
Bapat AA, Hostetter G, Von Hoff DD, Han H. Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer. 2011;11:695–707.
Google Scholar
Wang L, Xia Y, Jiang T, Li Y, Shen Y, Lin J, et al. Neural Invasion is an Independent Prognostic Factor in Young and Lymph Node Negative Gastric Cancer Patients Underwent Curative Gastrectomy. J Invest Surg. 2023;36:2257785.
Google Scholar
Zhao B, Lv W, Mei D, Luo R, Bao S, Huang B, et al. Perineural invasion as a predictive factor for survival outcome in gastric cancer patients: a systematic review and meta-analysis. J Clin Pathol. 2020;73:544–51.
Google Scholar
Wang W, Li L, Chen N, Niu C, Li Z, Hu J, et al. Nerves in the Tumor Microenvironment: Origin and Effects. Front Cell Dev Biol. 2020;8:601738.
Google Scholar
Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20:675–91.
Google Scholar
Cocquerelle C, Mascrez B, Hetuin D, Bailleul B. Mis-splicing yields circular RNA molecules. FASEB J. 1993;7:155–60.
Google Scholar
Kristensen LS, Jakobsen T, Hager H, Kjems J. The emerging roles of circRNAs in cancer and oncology. Nat Rev Clin Oncol. 2022;19:188–206.
Google Scholar
Dragomir MP, Kopetz S, Ajani JA, Calin GA. Non-coding RNAs in GI cancers: from cancer hallmarks to clinical utility. Gut. 2020;69:748–63.
Google Scholar
Liu X, Zhang Y, Zhou S, Dain L, Mei L, Zhu G. Circular RNA: An emerging frontier in RNA therapeutic targets, RNA therapeutics, and mRNA vaccines. J Control Release. 2022;348:84–94.
Google Scholar
Jagtap U, Anderson ES, Slack FJ. The Emerging Value of Circular Noncoding RNA Research in Cancer Diagnosis and Treatment. Cancer Res. 2023;83:809–13.
Google Scholar
Wu Z, Fang Z, Zeng L, Zhang D, Zhou Y, Chen R. RBMS1-mediates the biogenesis of circNFIB promotes perineural invasion of pancreatic ductal adenocarcinoma via the L1CAM/MAPK pathway. Theranostics. 2025;15:9261–78.
Google Scholar
Dai W, Wu X, Li J, Tang W, Wang Y, Xu W, et al. Hedgehog-Gli1-derived exosomal circ-0011536 mediates peripheral neural remodeling in pancreatic cancer by modulating the miR-451a/VGF axis. J Exp Clin Cancer Res. 2023;42:329.
Google Scholar
Gil Z, Kelly KJ, Brader P, Shah JP, Fong Y, Wong RJ. Utility of a herpes oncolytic virus for the detection of neural invasion by cancer. Neoplasia. 2008;10:347–53.
Google Scholar
Chen MM, Gao Q, Ning H, Chen K, Gao Y, Yu M, et al. Integrated single-cell and spatial transcriptomics uncover distinct cellular subtypes involved in neural invasion in pancreatic cancer. Cancer Cell. 2025;43:1656–1676.e1610.
Google Scholar
Qiu S, Li B, Xia Y, Xuan Z, Li Z, Xie L, et al. CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner. Cell Death Dis. 2022;13:266.
Google Scholar
Jiang SH, Zhang S, Wang H, Xue JL, Zhang ZG. Emerging experimental models for assessing perineural invasion in human cancers. Cancer Lett. 2022;535:215610.
Google Scholar
Xia Y, Jiang T, Li Y, Gu C, Lv J, Lu C, et al. circVAPA-rich small extracellular vesicles derived from gastric cancer promote neural invasion by inhibiting SLIT2 expression in neuronal cells. Cancer Lett. 2024;592:216926.
Google Scholar
Wu N, Yuan Z, Du KY, Fang L, Lyu J, Zhang C, et al. Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery. Cell Death Differ. 2019;26:2758–73.
Google Scholar
Reichert MC, Brown HE, Evans TA. In vivo functional analysis of Drosophila Robo1 immunoglobulin-like domains. Neural Dev. 2016;11:15.
Google Scholar
Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, et al. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell. 1999;96:795–806.
Google Scholar
Li HS, Chen JH, Wu W, Fagaly T, Zhou L, Yuan W, et al. Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons. Cell. 1999;96:807–18.
Google Scholar
Keleman K, Rajagopalan S, Cleppien D, Teis D, Paiha K, Huber LA, et al. Comm sorts robo to control axon guidance at the Drosophila midline. Cell. 2002;110:415–27.
Google Scholar
Myat A, Henry P, McCabe V, Flintoft L, Rotin D, Tear G. Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptor. Neuron. 2002;35:447–59.
Google Scholar
Crosas-Molist E, Samain R, Kohlhammer L, Orgaz JL, George SL, Maiques O, et al. Rho GTPase signaling in cancer progression and dissemination. Physiol Rev. 2022;102:455–510.
Google Scholar
Kong R, Yi F, Wen P, Liu J, Chen X, Ren J, et al. Myo9b is a key player in SLIT/ROBO-mediated lung tumor suppression. J Clin Invest. 2015;125:4407–20.
Google Scholar
Wong K, Ren XR, Huang YZ, Xie Y, Liu G, Saito H, et al. Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Cell. 2001;107:209–21.
Google Scholar
Bhosle VK, Mukherjee T, Huang YW, Patel S, Pang BWF, Liu GY, et al. SLIT2/ROBO1-signaling inhibits macropinocytosis by opposing cortical cytoskeletal remodeling. Nat Commun. 2020;11:4112.
Google Scholar
Kidd T, Brose K, Mitchell KJ, Fetter RD, Tessier-Lavigne M, Goodman CS, et al. Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell. 1998;92:205–15.
Google Scholar
Hoffman GR, Nassar N, Cerione RA. Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI. Cell. 2000;100:345–56.
Google Scholar
Garcia-Mata R, Boulter E, Burridge K. The ‘invisible hand’: regulation of RHO GTPases by RHOGDIs. Nat Rev Mol Cell Biol. 2011;12:493–504.
Google Scholar
DerMardirossian C, Schnelzer A, Bokoch GM. Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase. Mol Cell. 2004;15:117–27.
Google Scholar
Xiao Y, Lin VY, Ke S, Lin GE, Lin FT, Lin WC. 14-3-3τ promotes breast cancer invasion and metastasis by inhibiting RhoGDIα. Mol Cell Biol. 2014;34:2635–49.
Google Scholar
Cho HJ, Kim JT, Lee SJ, Hwang YS, Park SY, Kim BY, et al. Protein phosphatase 1B dephosphorylates Rho guanine nucleotide dissociation inhibitor 1 and suppresses cancer cell migration and invasion. Cancer Lett. 2018;417:141–51.
Google Scholar
Chen LL. The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016;17:205–11.
Google Scholar
Kim M, Kim JH, Baek SJ, Kim SY, Kim YS. Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes. Int J Oncol. 2016;48:2497–507.
Google Scholar
Tseng RC, Chang JM, Chen JH, Huang WR, Tang YA, Kuo IY, et al. Deregulation of SLIT2-mediated Cdc42 activity is associated with esophageal cancer metastasis and poor prognosis. J Thorac Oncol. 2015;10:189–98.
Google Scholar
Huang Z, Wen P, Kong R, Cheng H, Zhang B, Quan C, et al. USP33 mediates Slit-Robo signaling in inhibiting colorectal cancer cell migration. Int J Cancer. 2015;136:1792–802.
Google Scholar
Zahalka AH, Frenette PS. Nerves in cancer. Nat Rev Cancer. 2020;20:143–57.
Google Scholar
Vaes N, Idris M, Boesmans W, Alves MM, Melotte V. Nerves in gastrointestinal cancer: from mechanism to modulations. Nat Rev Gastroenterol Hepatol. 2022;19:768–84.
Google Scholar
Winkler F, Venkatesh HS, Amit M, Batchelor T, Demir IE, Deneen B, et al. Cancer neuroscience: State of the field, emerging directions. Cell. 2023;186:1689–707.
Google Scholar
Mancusi R, Monje M. The neuroscience of cancer. Nature. 2023;618:467–79.
Google Scholar
Zhi X, Wu F, Qian J, Ochiai Y, Lian G, Malagola E, et al. Nociceptive neurons promote gastric tumour progression via a CGRP-RAMP1 axis. Nature. 2025;640:802–10.
Google Scholar
Wang K, Ni B, Xie Y, Li Z, Yuan L, Meng C, et al. Nociceptor neurons promote PDAC progression and cancer pain by interaction with cancer-associated fibroblasts and suppression of natural killer cells. Cell Res. 2025;35:362–80.
Google Scholar
Baruch EN, Gleber-Netto FO, Nagarajan P, Rao X, Akhter S, Eichwald T, et al. Cancer-induced nerve injury promotes resistance to anti-PD-1 therapy. Nature 2025;646:462–73.
Wang SM, Tie J, Wang WL, Hu SJ, Yin JP, Yi XF, et al. POU2F2-oriented network promotes human gastric cancer metastasis. Gut. 2016;65:1427–38.
Google Scholar
Li Q, Zhang XX, Hu LP, Ni B, Li DX, Wang X, et al. Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma. Nat Commun. 2023;14:861.
Google Scholar
Ahirwar DK, Charan M, Mishra S, Verma AK, Shilo K, Ramaswamy B, et al. Slit2 Inhibits Breast Cancer Metastasis by Activating M1-Like Phagocytic and Antifibrotic Macrophages. Cancer Res. 2021;81:5255–67.
Google Scholar
Gohrig A, Detjen KM, Hilfenhaus G, Korner JL, Welzel M, Arsenic R, et al. Axon guidance factor SLIT2 inhibits neural invasion and metastasis in pancreatic cancer. Cancer Res. 2014;74:1529–40.
Google Scholar
Huang D, Zhu X, Ye S, Zhang J, Liao J, Zhang N, et al. Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides. Nature. 2024;625:593–602.
Google Scholar
Yi Q, Feng J, Lan W, Shi H, Sun W, Sun W. CircRNA and lncRNA-encoded peptide in diseases, an update review. Mol Cancer. 2024;23:214.
Google Scholar
Jiang T, Xia Y, Lv J, Li B, Li Y, Wang S, et al. A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling. Mol Cancer. 2021;20:66.
Google Scholar
Xia X, Li X, Li F, Wu X, Zhang M, Zhou H, et al. A novel tumor suppressor protein encoded by circular AKT3 RNA inhibits glioblastoma tumorigenicity by competing with active phosphoinositide-dependent Kinase-1. Mol Cancer. 2019;18:131.
Google Scholar
Liang WC, Wong CW, Liang PP, Shi M, Cao Y, Rao ST, et al. Translation of the circular RNA circβ-catenin promotes liver cancer cell growth through activation of the Wnt pathway. Genome Biol. 2019;20:84.
Google Scholar
Tavora B, Mederer T, Wessel KJ, Ruffing S, Sadjadi M, Missmahl M, et al. Tumoural activation of TLR3-SLIT2 axis in endothelium drives metastasis. Nature 2020;586:299–304.
Google Scholar
Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012;491:399–405.
Google Scholar
Sahai E, Marshall CJ. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nat Cell Biol. 2003;5:711–9.
Google Scholar
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014;513:202–9.
Cho HJ, Kim JT, Baek KE, Kim BY, Lee HG. Regulation of Rho GTPases by RhoGDIs in Human Cancers. Cells 2019;8:1037.
Liu R, Zhao E, Yu H, Yuan C, Abbas MN, Cui H. Methylation across the central dogma in health and diseases: new therapeutic strategies. Signal Transd Target Ther. 2023;8:310.
Google Scholar
Nishiyama A, Nakanishi M. Navigating the DNA methylation landscape of cancer. Trends Genet. 2021;37:1012–27.
Google Scholar
Davalos V, Esteller M. Cancer epigenetics in clinical practice. CA Cancer J Clin. 2023;73:376–424.
Google Scholar
Zhang J, Li H, Niswander LA. m(5)C methylated lncRncr3-MeCP2 interaction restricts miR124a-initiated neurogenesis. Nat Commun. 2024;15:5136.
Google Scholar
Zhao S, Hao S, Zhou J, Chen X, Zhang T, Qi Z, et al. mTOR/miR-142-3p/PRAS40 signaling cascade is critical for tuberous sclerosis complex-associated renal cystogenesis. Cell Mol Biol Lett. 2024;29:125.
Google Scholar
