ArticleThe Journal of clinical investigation2018
The BRG1/SOX9 axis is critical for acinar cell-derived pancreatic tumorigenesis.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- Acinar-ductal metaplasia in pancreatitis and pancreatic ductal adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Polybromo 1/vimentin axis dictates tumor grade, epithelial-mesenchymal transition, and metastasis in pancreatic cancer.The Journal of clinical investigation · 2025Article
- Protocol for chromatin immunoprecipitation of chromatin-binding proteins in Schizosaccharomyces pombe using a dual-crosslinking approach.STAR protocols · 2025Article
- BRG1 promotes liver cancer cell proliferation and metastasis by enhancing mitochondrial function and ATP5A1 synthesis through TOMM40.Cancer biology & therapy · 2024Article
- FRA1 controls acinar cell plasticity during murine KrasDevelopmental cell · 2024Article
- DKK1-SE recruits AP1 to activate the target gene DKK1 thereby promoting pancreatic cancer progression.Cell death & disease · 2024Article
- Advances in the study of the role of high-frequency mutant subunits of the SWI/SNF complex in tumors.Frontiers in oncology · 2024Review
- Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer.International journal of molecular sciences · 2023Review
- Brg1 controls stemness and metastasis of pancreatic cancer through regulating hypoxia pathway.Oncogene · 2023Article
- BRG1: Promoter or Suppressor of Cancer? The Outcome of BRG1's Interaction with Specific Cellular Pathways.International journal of molecular sciences · 2023Review
- Epigenetic reprogramming in pancreatic premalignancy and clinical implications.Frontiers in oncology · 2023Review
- JNK pathway plays a critical role for expansion of human colorectal cancer in the context of BRG1 suppression.Cancer science · 2022Article
- Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis.National science review · 2022Article
- Exosomal microRNAs shuttling between tumor cells and macrophages: cellular interactions and novel therapeutic strategies.Cancer cell international · 2022Review
- Stem Cell-Derived Islets for Type 2 Diabetes.International journal of molecular sciences · 2022Review
- In situ vaccination using unique TLR9 ligand K3-SPG induces long-lasting systemic immune response and synergizes with systemic and local immunotherapy.Scientific reports · 2022Article
- Cell Type of Pancreatic Ductal Adenocarcinoma Origin: Implications for Prognosis and Clinical Outcomes.Visceral medicine · 2022Review
- Prognostic value ofFrontiers in genetics · 2022Article
- Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Review of Their Genetic Characteristics and Mouse Models.Cancers · 2021Review
- Review
Corrections and comments
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Authors and funding
26 authors at 5 institutions in 3 countries.
Funding
Abstract
Chromatin remodeler Brahma related gene 1 (BRG1) is silenced in approximately 10% of human pancreatic ductal adenocarcinomas (PDAs). We previously showed that BRG1 inhibits the formation of intraductal pancreatic mucinous neoplasm (IPMN) and that IPMN-derived PDA originated from ductal cells. However, the role of BRG1 in pancreatic intraepithelial neoplasia-derived (PanIN-derived) PDA that originated from acinar cells remains elusive. Here, we found that exclusive elimination of Brg1 in acinar cells of Ptf1a-CreER; KrasG12D; Brg1fl/fl mice impaired the formation of acinar-to-ductal metaplasia (ADM) and PanIN independently of p53 mutation, while PDA formation was inhibited in the presence of p53 mutation. BRG1 bound to regions of the Sox9 promoter to regulate its expression and was critical for recruitment of upstream regulators, including PDX1, to the Sox9 promoter and enhancer in acinar cells. SOX9 expression was downregulated in BRG1-depleted ADMs/PanINs. Notably, Sox9 overexpression canceled this PanIN-attenuated phenotype in KBC mice. Furthermore, Brg1 deletion in established PanIN by using a dual recombinase system resulted in regression of the lesions in mice. Finally, BRG1 expression correlated with SOX9 expression in human PDAs. In summary, BRG1 is critical for PanIN initiation and progression through positive regulation of SOX9. Thus, the BRG1/SOX9 axis is a potential target for PanIN-derived PDA.
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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.