SMARCA4 activation engages FOSL1 to drive enhancer reprogramming and tumorigenic phenotypes in SMARCA4-deficient LUAD cells

Ren G, Ku WL, Ge G, Hoffman JA, Kang JY, Tang Q, et al. Acute depletion of BRG1 reveals its primary function as an activator of transcription. Nat Commun. 2024;15:4561.

Google Scholar 

Längst G, Manelyte L. Chromatin remodelers: from function to dysfunction. Genes. 2015;6:299–324.

Google Scholar 

Basurto-Cayuela L, Guerrero-Martínez JA, Gómez-Marín E, Sánchez-Escabias E, Escaño-Maestre M, Ceballos-Chávez M, et al. SWI/SNF-dependent genes are defined by their chromatin landscape. Cell Reports. 2024;43:113855.

Iurlaro M, Stadler MB, Masoni F, Jagani Z, Galli GG, Schübeler D. Mammalian SWI/SNF continuously restores local accessibility to chromatin. Nat Genet. 2021;53:279–87.

Google Scholar 

Hargreaves DC. Chromatin openness requires continuous SWI/SNF activity. Nat Genet. 2021;53:263–4.

Google Scholar 

Hargreaves DC, Crabtree GR. ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res. 2011;21:396–420.

Google Scholar 

Kadoch C, Crabtree GR. Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics. Sci Adv. 2015;1:e1500447.

Google Scholar 

Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, et al. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet. 2013;45:592–601.

Google Scholar 

Mittal P, Roberts CW. The SWI/SNF complex in cancer—biology, biomarkers and therapy. Nat Rev Clin Oncol. 2020;17:435–48.

Google Scholar 

Liu W, Kurkewich JL, Stoddart A, Khan S, Anandan D, Gaubil AN, et al. CUX1 regulates human hematopoietic stem cell chromatin accessibility via the BAF complex. Cell Rep. 2024;43:114227.

Hodges HC, Stanton BZ, Cermakova K, Chang C-Y, Miller EL, Kirkland JG, et al. Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue-unrestricted enhancers. Nat Struct Mol Biol. 2018;25:61–72.

Google Scholar 

Zhao J, Zhu J, Tang Y, Zheng K, Li Z. Advances in the study of the role of high-frequency mutant subunits of the SWI/SNF complex in tumors. Front Oncol. 2024;14:1463892.

Google Scholar 

Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 2011;11:481–92.

Google Scholar 

Yao B, Gui T, Zeng X, Deng Y, Wang Z, Wang Y, et al. PRMT1-mediated H4R3me2a recruits SMARCA4 to promote colorectal cancer progression by enhancing EGFR signaling. Genome Med. 2021;13:1–21.

Google Scholar 

Muthuswami R, Bailey L, Rakesh R, Imbalzano AN, Nickerson JA, Hockensmith JW. BRG1 is a prognostic indicator and a potential therapeutic target for prostate cancer. J Cell Physiol. 2019;234:15194–205.

Google Scholar 

Guerrero-Martínez JA, Reyes JC. High expression of SMARCA4 or SMARCA2 is frequently associated with an opposite prognosis in cancer. Sci Rep. 2018;8:2043.

Google Scholar 

Peng L, Li J, Wu J, Xu B, Wang Z, Giamas G, et al. A pan-cancer analysis of SMARCA4 alterations in human cancers. Front Immunol. 2021;12:762598.

Google Scholar 

Mardinian K, Adashek JJ, Botta GP, Kato S, Kurzrock R. SMARCA4: implications of an altered chromatin-remodeling gene for cancer development and therapy. Mol Cancer Ther. 2021;20:2341–51.

Google Scholar 

Long HK, Prescott SL, Wysocka J. Ever-changing landscapes: transcriptional enhancers in development and evolution. Cell. 2016;167:1170–87.

Google Scholar 

Maston GA, Evans SK, Green MR. Transcriptional regulatory elements in the human genome. Annu Rev Genom Hum Genet. 2006;7:29–59.

Google Scholar 

Jones CA, Tansey WP, Weissmiller AM. Emerging themes in mechanisms of tumorigenesis by SWI/SNF subunit mutation. Epigenet Insights. 2022;15:25168657221115656.

Google Scholar 

Bulger M, Groudine M. Functional and mechanistic diversity of distal transcription enhancers. Cell. 2011;144:327–39.

Google Scholar 

Zboril E, Yoo H, Chen L, Liu Z. Dynamic interactions of transcription factors and enhancer reprogramming in cancer progression. Front Oncol. 2021;11:753051.

Google Scholar 

Andersson R, Sandelin A. Determinants of enhancer and promoter activities of regulatory elements. Nat Rev Genet. 2020;21:71–87.

Google Scholar 

Zaret KS, Carroll JS. Pioneer transcription factors: establishing competence for gene expression. Genes Dev. 2011;25:2227–41.

Google Scholar 

Spitz F, Furlong EE. Transcription factors: from enhancer binding to developmental control. Nat Rev Genet. 2012;13:613–26.

Google Scholar 

Iwafuchi-Doi M, Zaret KS. Pioneer transcription factors in cell reprogramming. Genes Dev. 2014;28:2679–92.

Google Scholar 

Reiter F, Wienerroither S, Stark A. Combinatorial function of transcription factors and cofactors. Curr Opin Genet Dev. 2017;43:73–81.

Google Scholar 

Alver BH, Kim KH, Lu P, Wang X, Manchester HE, Wang W, et al. The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers. Nat Commun. 2017;8:14648.

Google Scholar 

Yao J, Chen J, Li L-Y, Wu M. Epigenetic plasticity of enhancers in cancer. Transcription. 2020;11:26–36.

Google Scholar 

Morgan MA, Shilatifard A. Chromatin signatures of cancer. Genes Dev. 2015;29:238–49.

Google Scholar 

Abatti LE, Lado-Fernández P, Huynh L, Collado M, Hoffman MM, Mitchell JA. Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma. Nucleic Acids Res. 2023;51:10109–31.

Google Scholar 

Fu X, Pereira R, De Angelis C, Veeraraghavan J, Nanda S, Qin L, et al. FOXA1 upregulation promotes enhancer and transcriptional reprogramming in endocrine-resistant breast cancer. Proc Natl Acad Sci. 2019;116:26823–34.

Google Scholar 

Li R, Wang H, Bekele B, Yin Z, Caraway N, Katz R, et al. Identification of putative oncogenes in lung adenocarcinoma by a comprehensive functional genomic approach. Oncogene. 2006;25:2628–35.

Google Scholar 

Pan J, McKenzie ZM, D’Avino AR, Mashtalir N, Lareau CA, St. Pierre R, et al. The ATPase module of mammalian SWI/SNF family complexes mediates subcomplex identity and catalytic activity–independent genomic targeting. Nat Genet. 2019;51:618–26.

Google Scholar 

Barutcu AR, Lajoie BR, Fritz AJ, McCord RP, Nickerson JA, Van Wijnen AJ, et al. SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells. Genome Res. 2016;26:1188–201.

Google Scholar 

Wolf BK, Zhao Y, McCray A, Hawk WH, Deary LT, Sugiarto NW, et al. Cooperation of chromatin remodeling SWI/SNF complex and pioneer factor AP-1 shapes 3D enhancer landscapes. Nat Struct Mol Biol. 2023;30:10–21.

Google Scholar 

Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38:576–89.

Google Scholar 

Vierbuchen T, Ling E, Cowley CJ, Couch CH, Wang X, Harmin DA, et al. AP-1 transcription factors and the BAF complex mediate signal-dependent enhancer selection. Mol Cell. 2017;68:1067–82.e12.

Google Scholar 

Farnaby W, Koegl M, Roy MJ, Whitworth C, Diers E, Trainor N, et al. BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design. Nat Chem Biol. 2019;15:672–80.

Google Scholar 

Papillon JP, Nakajima K, Adair CD, Hempel J, Jouk AO, Karki RG, et al. Discovery of orally active inhibitors of brahma homolog (BRM)/SMARCA2 ATPase activity for the treatment of brahma related gene 1 (BRG1)/SMARCA4-mutant cancers. J Med Chem. 2018;61:10155–72.

Google Scholar 

Helming KC, Wang X, Roberts CW. Vulnerabilities of mutant SWI/SNF complexes in cancer. Cancer cell. 2014;26:309–17.

Google Scholar 

Wu Q, Madany P, Dobson JR, Schnabl JM, Sharma S, Smith TC, et al. The BRG1 chromatin remodeling enzyme links cancer cell metabolism and proliferation. Oncotarget. 2016;7:38270.

Google Scholar 

Orvis T, Hepperla A, Walter V, Song S, Simon J, Parker J, et al. BRG1/SMARCA4 inactivation promotes non–small cell lung cancer aggressiveness by altering chromatin organization. Cancer Res. 2014;74:6486–98.

Google Scholar 

Naito T, Udagawa H, Umemura S, Sakai T, Zenke Y, Kirita K, et al. Non-small cell lung cancer with loss of expression of the SWI/SNF complex is associated with aggressive clinicopathological features, PD-L1-positive status, and high tumor mutation burden. Lung Cancer. 2019;138:35–42.

Google Scholar 

Redin E, Sridhar H, Zhan YA, Pereira Mello B, Zhong H, Durani V, et al. SMARCA4 controls state plasticity in small cell lung cancer through regulation of neuroendocrine transcription factors and REST splicing. J Hematol Oncol. 2024;17:58.

Google Scholar 

Wang L-H, Aberin MAE, Wu S, Wang S-P. The MLL3/4 H3K4 methyltransferase complex in establishing an active enhancer landscape. Biochem Soc Trans. 2021;49:1041–54.

Google Scholar 

Park Y-K, Lee J-E, Yan Z, McKernan K, O’Haren T, Wang W, et al. Interplay of BAF and MLL4 promotes cell type-specific enhancer activation. Nat Commun. 2021;12:1630.

Google Scholar 

Fonseca GJ, Tao J, Westin EM, Duttke SH, Spann NJ, Strid T, et al. Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages. Nat Commun. 2019;10:414.

Google Scholar 

Lopez-Bergami P, Lau E, Ronai Ze. Emerging roles of ATF2 and the dynamic AP1 network in cancer. Nat Rev Cancer. 2010;10:65–76.

Google Scholar 

Jiang SS, Fang W-T, Hou Y-H, Huang S-F, Yen BL, Chang J-L, et al. Upregulation of SOX9 in lung adenocarcinoma and its involvement in the regulation of cell growth and tumorigenicity. Clin Cancer Res. 2010;16:4363–73.

Google Scholar 

Fan W, Xing Y, Yan S, Liu W, Ning J, Tian F, et al. DUSP5 regulated by YTHDF1-mediated m6A modification promotes epithelial-mesenchymal transition and EGFR-TKI resistance via the TGF-β/Smad signaling pathway in lung adenocarcinoma. Cancer Cell Int. 2024;24:208.

Google Scholar 

Lin Z, Lin X, Zhu L, Huang J, Huang Y. TRIM2 directly deubiquitinates and stabilizes Snail1 protein, mediating proliferation and metastasis of lung adenocarcinoma. Cancer Cell Int. 2020;20:1–14.

Google Scholar 

Relli V, Trerotola M, Guerra E, Alberti S. Abandoning the notion of non-small cell lung cancer. Trends Mol Med. 2019;25:585–94.

Google Scholar 

Regina S, Valentin J-B, Lachot SB, Lemarié E, Rollin J, Gruel Y. Increased tissue factor expression is associated with reduced survival in non–small cell lung cancer and with mutations of TP53 and PTEN. Clin Chem. 2009;55:1834–42.

Google Scholar 

Zhang L, Huang P, Huang C, Jiang L, Lu Z, Wang P. Varied clinical significance of ATP-binding cassette C sub-family members for lung adenocarcinoma. Medicine. 2021;100:e25246.

Google Scholar 

Li Q, Liu X-L, Jiang N, Li Q-Y, Song Y-X, Ke X-X, et al. A new prognostic model for RHOV, ABCC2, and CYP4B1 to predict the prognosis and association with immune infiltration of lung adenocarcinoma. J Thorac Dis. 2023;15:1919.

Google Scholar 

Ma Q, Xiao F, Hao Y, Song Z, Zhang J, Si C, et al. The prognostic role of the Transducin-like Enhancer of split protein family in lung adenocarcinoma. Transl Lung Cancer Res. 2021;10:3251.

Google Scholar 

He D, Tang H, Yang X, Liu X, Zhang Y, Shi J. Elaboration and validation of a prognostic signature associated with disulfidoptosis in lung adenocarcinoma, consolidated with integration of single-cell RNA sequencing and bulk RNA sequencing techniques. Front Immunol. 2023;14:1278496.

Google Scholar 

Qiu Z-X, Zhao S, Mo X-M, Li W-M. Overexpression of PROM1 (CD133) confers poor prognosis in non-small cell lung cancer. Int J Clin Exp Pathol. 2015;8:6589.

Google Scholar 

Saha SK, Islam SR, Kwak K-S, Rahman MS, Cho S-G. PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis. Cancer Gene Ther. 2020;27:147–67.

Google Scholar 

Roh W, Geffen Y, Cha H, Miller M, Anand S, Kim J, et al. High-resolution profiling of lung adenocarcinoma identifies expression subtypes with specific biomarkers and clinically relevant vulnerabilities. Cancer Res. 2022;82:3917–31.

Google Scholar 

Reis H, Metzenmacher M, Goetz M, Savvidou N, Darwiche K, Aigner C, et al. MET expression in advanced non–small-cell lung cancer: effect on clinical outcomes of chemotherapy, targeted therapy, and immunotherapy. Clin Lung Cancer. 2018;19:e441–e63.

Google Scholar 

Ma PC, Tretiakova MS, MacKinnon AC, Ramnath N, Johnson C, Dietrich S, et al. Expression and mutational analysis of MET in human solid cancers. Genes Chromosom Cancer. 2008;47:1025–37.

Google Scholar 

Hafner A, Boettiger A. The spatial organization of transcriptional control. Nat Rev Genet. 2023;24:53–68.

Google Scholar 

Reddy KL, Feinberg AP. Higher order chromatin organization in cancer. Semin Cancer Biol. 2013;23:109–15.

Deng S, Feng Y, Pauklin S. 3D chromatin architecture and transcription regulation in cancer. J Hematol Oncol. 2022;15:49.

Google Scholar 

Kim T, Han S, Chun Y, Yang H, Min H, Jeon SY, et al. Comparative characterization of 3D chromatin organization in triple-negative breast cancers. Exp Mol Med. 2022;54:585–600.

Google Scholar 

Song S, Jeon M, Nam J, Kang J, Lee Y, Kang J, et al. Aberrant GATA2 epigenetic dysregulation induces a GATA2/GATA6 switch in human gastric cancer. Oncogene. 2018;37:993–1004.

Google Scholar 

Kim H, Han S, Song S, Jeong E, Lee M, Hwang D, et al. Testican-1-mediated epithelial–mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer. Oncogene. 2014;33:3334–41.

Google Scholar 

Yun J, Song S-H, Kang J-Y, Park J, Kim H-P, Han S-W, et al. Reduced cohesin destabilizes high-level gene amplification by disrupting pre-replication complex bindings in human cancers with chromosomal instability. Nucleic Acids Res. 2016;44:558–72.

Google Scholar 

Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods. 2013;10:1213–8.

Google Scholar 

Corces MR, Trevino AE, Hamilton EG, Greenside PG, Sinnott-Armstrong NA, Vesuna S, et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat Methods. 2017;14:959–62.

Google Scholar 

Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinforma. 2013;14:128.

Google Scholar 

Xie Z, Bailey A, Kuleshov MV, Clarke DJ, Evangelista JE, Jenkins SL, et al. Gene set knowledge discovery with Enrichr. Curr Protoc. 2021;1:e90.

Google Scholar 

Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44:W90–W7.

Google Scholar