{"doi":"10.1172/jci94287","title":"The BRG1/SOX9 axis is critical for acinar cell–derived pancreatic tumorigenesis","abstract":null,"journal":"Journal of Clinical Investigation","year":2018,"id":648136,"datarank":2.135438098643071,"base_score":4.060443010546419,"endowment":4.060443010546419,"self_citation_contribution":0.6090664515819629,"citation_network_contribution":1.5263716470611084,"self_endowment_contribution":0.6090664515819629,"citer_contribution":1.5263716470611084,"corpus_percentile":null,"corpus_rank":null,"citation_count":57,"citer_count":50,"citers_with_citation_signal":47,"citers_with_endowment":47,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1688923,"name":"Akihisa Fukuda","orcid":null,"position":1,"is_corresponding":false},{"id":564460,"name":"Nilotpal Roy","orcid":"0009-0009-9899-0092","position":2,"is_corresponding":false},{"id":1688924,"name":"Yukiko Hiramatsu","orcid":"0000-0001-5903-8677","position":3,"is_corresponding":false},{"id":1688925,"name":"Laura Leonhardt","orcid":null,"position":4,"is_corresponding":false},{"id":639136,"name":"Nobuyuki Kakiuchi","orcid":"0000-0003-4893-5414","position":5,"is_corresponding":false},{"id":1688926,"name":"Kaja Hoyer","orcid":null,"position":6,"is_corresponding":false},{"id":1378289,"name":"Satoshi Ogawa","orcid":"0000-0002-4790-546X","position":7,"is_corresponding":false},{"id":861404,"name":"Norihiro Goto","orcid":null,"position":8,"is_corresponding":false},{"id":1688927,"name":"Kozo Ikuta","orcid":null,"position":9,"is_corresponding":false},{"id":1688928,"name":"Yoshito Kimura","orcid":null,"position":10,"is_corresponding":false},{"id":1688929,"name":"Yoshihide Matsumoto","orcid":null,"position":11,"is_corresponding":false},{"id":1688930,"name":"Yutaka Takada","orcid":null,"position":12,"is_corresponding":false},{"id":1688931,"name":"Takuto Yoshioka","orcid":null,"position":13,"is_corresponding":false},{"id":1688932,"name":"Takahisa Maruno","orcid":null,"position":14,"is_corresponding":false},{"id":1688933,"name":"Yuichi Yamaga","orcid":null,"position":15,"is_corresponding":false},{"id":1652542,"name":"Grace E. 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Wright","orcid":null,"position":19,"is_corresponding":false},{"id":56162,"name":"Dieter Saur","orcid":"0000-0001-5874-0210","position":20,"is_corresponding":false},{"id":1688938,"name":"Kyoichi Takaori","orcid":null,"position":21,"is_corresponding":false},{"id":1600367,"name":"Shinji Uemoto","orcid":null,"position":22,"is_corresponding":false},{"id":320874,"name":"Matthias Hebrok","orcid":"0000-0002-3833-8862","position":23,"is_corresponding":false},{"id":139799,"name":"Tsutomu Chiba","orcid":null,"position":24,"is_corresponding":false},{"id":1573048,"name":"Hiroshi Seno","orcid":null,"position":25,"is_corresponding":false},{"id":990295,"name":"Motoyuki Tsuda","orcid":"0000-0003-2873-1449","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The BRG1/SOX9 axis is critical for acinar cell–derived pancreatic tumorigenesis","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.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19162232","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"Grants-in-Aid KAKENHI","grant_id":"25112707,26293173,14J03460,16K09394,16K15427","title":null},{"funder_name":"Kobayashi Foundation for Cancer Research","grant_id":"no number","title":null},{"funder_name":"Princess Takamatsu Cancer Reseach","grant_id":"13-24514","title":null},{"funder_name":"NCI","grant_id":"RO1CA172045","title":null},{"funder_name":"European Commission","grant_id":"648521","title":"Next-generation in vivo models for improved pancreatic cancer therapies"}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":null,"oa_locations":[{"url":"http://www.jci.org/articles/view/94287/files/pdf","host_type":"publisher"},{"url":"https://www.jci.org/articles/view/94287/files/pdf","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6063489","host_type":"repository"},{"url":"https://doi.org/10.1172/jci94287","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/30010625","host_type":""},{"url":"https://dx.doi.org/10.1172/jci94287","host_type":""},{"url":"https://escholarship.org/uc/item/346483p1","host_type":""},{"url":"http://dx.doi.org/10.1172/jci94287","host_type":""},{"url":"https://doi.org/https://doi.org/10.1172/jci94287","host_type":""}],"fields_of_study":["0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Male","Immunology","Mice, Transgenic","Cell Transformation","Mouse models","Response Elements","Medical and Health Sciences","Transgenic","Pancreatic Cancer","Mice","Rare Diseases","Genetics","2.1 Biological and endogenous factors","Animals","Humans","Aetiology","Cancer","Neoplastic","Carcinoma","Gastroenterology","DNA Helicases","Nuclear Proteins","SOX9 Transcription Factor","Pancreatic Neoplasms","Cell Transformation, Neoplastic","Oncology","Gene Expression Regulation","Pancreatic Ductal","Epigenetics","Female","Tumor Suppressor Protein p53","Digestive Diseases","Carcinoma, Pancreatic Ductal","Signal Transduction","Transcription Factors"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. 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