ArticleEMBO molecular medicine2012
The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 95 citations in OpenAlex.
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Precise modulation of BRG1 levels reveals features of mSWI/SNF dosage sensitivity.Nature genetics · 2025Article
- The role of SMARCA4 in lung cancer.Scientific reports · 2025Review
- MYC Regulates a DNA Repair Gene Expression Program in Small Cell Carcinoma of the Ovary, Hypercalcemic Type.Cancers · 2025Article
- Thoracic SMARCA4-deficient undifferentiated tumor: diagnostic characteristics, molecular insights, and treatment approaches.The oncologist · 2025Article
- Review
- Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.Virchows Archiv : an international journal of pathology · 2025Article
- Efficacy of glutathione inhibitor eprenetapopt against the vulnerability of glutathione metabolism in SMARCA4-, SMARCB1- and PBRM1-deficient cancer cells.Scientific reports · 2024Article
- Preclinical evidence in the assembly of mammalian SWI/SNF complexes: Epigenetic insights and clinical perspectives in human lung disease therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- The golden key to open mystery boxes of SMARCA4-deficient undifferentiated thoracic tumor: focusing immunotherapy, tumor microenvironment and epigenetic regulation.Cancer gene therapy · 2024Review
- Treatment of Thoracic SMARCA4-Deficient Undifferentiated Tumors: Where We Are and Where We Will Go.International journal of molecular sciences · 2024Review
- Case report: Aggressive NSCLC with partial BRG-1 deficiency and KRAS G12C mutation: a case study and treatment challenges.Frontiers in oncology · 2024Article
- Esophageal carcinoma withTranslational gastroenterology and hepatology · 2024Review
- Targeting the TCA cycle through cuproptosis confers synthetic lethality on ARID1A-deficient hepatocellular carcinoma.Cell reports. Medicine · 2023Article
- [SWI/SNF Complex Gene Mutations Promote the Liver Metastasis of Non-small Cell Lung Cancer Cells in NSI Mice].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Dysregulation of SWI/SNF Chromatin Remodelers in NSCLC: Its Influence on Cancer Therapies including Immunotherapy.Biomolecules · 2023Review
- Thoracic SMARCA4-deficient undifferentiated tumor.Discover oncology · 2023Review
- MiR-6511b-5p suppresses metastasis of pMMR colorectal cancer through methylation of CD44 by directly targeting BRG1.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- [Analysis of Clinicopathologic Features of 9 Cases of SMARCA4-deficient Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Article
- Molecular targeted therapies for pediatric atypical teratoid/rhabdoid tumors.Pediatric investigation · 2022Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
BRG1, a member of the SWI/SNF complex, is mutated in cancer, but it is unclear how it promotes tumourigenesis. We report that re-expression of BRG1 in lung cancer cells up-regulates lung-specific transcripts, restoring the gene expression signature of normal lung. Using cell lines from several cancer types we found that those lacking BRG1 do not respond to retinoic acid (RA) or glucocorticoids (GC), while restoration of BRG1 restores sensitivity. Conversely, in SH-SY5Y cells, a paradigm of RA-dependent differentiation, abrogation of BRG1 prevented the response to RA. Further, our data suggest an antagonistic functional connection between BRG1 and MYC, whereby, refractoriness to RA and GC by BRG1 inactivation involves deregulation of MYC activity. Mechanistically, some of these effects are mediated by BRG1 binding to MYC and MYC-target promoters. The BRG1-MYC antagonism was also evident in primary tumours. Finally, BRG1 restoration significantly dampened invasion and progression and decreased MYC in lung cancer cells orthotopically implanted in nude mice. Thus, BRG1 inactivation enables cancer cells to sustain undifferentiated gene expression programs and prevent its response to environmental stimuli.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.