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In this study, we demonstrated that pancreas-specific loss of\n                    <jats:italic>Pbrm1<\/jats:italic>\n                    in mice harboring\n                    <jats:italic>Kras<\/jats:italic>\n                    mutations and\n                    <jats:italic>Trp53<\/jats:italic>\n                    deletions accelerated the development of poorly differentiated PDAC, epithelial-mesenchymal transition (EMT), and metastasis, resulting in worsened prognosis.\n                    <jats:italic>Pbrm1<\/jats:italic>\n                    loss in preexisting PDAC shifted the tumor grade from a well- to a poorly differentiated state and elevated vimentin expression.\n                    <jats:italic>Pbrm1<\/jats:italic>\n                    -null PDAC exhibited downregulation of apical junction genes and upregulation of EMT pathway genes, including the vimentin and squamous molecular subtype signature genes. Mechanistically, PBRM1 bound to the vimentin gene promoter and directly downregulated its expression. Furthermore, suppression of vimentin in\n                    <jats:italic>Pbrm1<\/jats:italic>\n                    -null PDAC cells reversed the dedifferentiation phenotype and reduced EMT and metastasis. Consistently, reduced PBRM1 expression correlated with high vimentin expression, poorly differentiated histology, a high recurrence rate, and reduced overall survival in human PDACs. Additionally, PDAC with\n                    <jats:italic>PBRM1<\/jats:italic>\n                    deletion was associated with the aggressive squamous molecular subtype. Our data established PBRM1 as a tumor suppressor that controls tumor grade and metastasis of PDAC by regulating vimentin expression.\n                  <\/jats:p>","DOI":"10.1172\/jci177533","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T14:00:41Z","timestamp":1748786441000},"source":"Crossref","is-referenced-by-count":13,"title":["Polybromo 1\/vimentin axis dictates tumor grade, epithelial-mesenchymal transition, and metastasis in pancreatic cancer"],"prefix":"10.1172","volume":"135","author":[{"given":"Munenori","family":"Kawai","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1940-596X","authenticated-orcid":true,"given":"Akihisa","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology 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