{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Antonucci L"],"funding":["NCI NIH HHS"],"pagination":["1263-1282"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12331375"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(7)"],"pubmed_abstract":["Pancreatic ductal adenocarcinoma (PDAC) emerges from mutant KRAS-harboring but dormant low-grade pancreatic intraepithelial neoplasia (PanIN). To examine the role of oxidative stress, a putative PDAC risk factor, we established an organoid-based transformation system. Although the prototypic oxidant H<sub>2</sub>O<sub>2</sub> induced organoid transformation, its effect was nonmutational and was mediated by the oxidant-responsive transcription factor NRF2, which induced the histone methyltransferase EZH2. Congruently, nonoxidizing NRF2 activators triggered organoid malignant conversion through NRF2 and EZH2, establishing a hitherto unknown epigenetic mechanism underlying PanIN-to-PDAC progression. While NRF2 induced EZH2 gene transcription in mouse and human PDAC, EZH2, a general repressor,"],"journal":["Nature cancer"],"pubmed_title":["Self-amplifying NRF2-EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer."],"pmcid":["PMC12331375"],"funding_grant_id":["P01 CA281819","U01 CA274295"],"pubmed_authors":["Rundberg Nilsson A","Eibl G","Nandi SP","Moscat J","Hu Y","Waugh T","Krawczyk M","Tsuda M","Tamayo P","Sanchez-Lopez E","Dawson DW","Bar-Sagi D","Zhao Y","Glass CK","Puri PL","Liu Y","Hatzivassiliou G","Roose-Girma M","Shah VM","Gu L","Caputo L","Cobo I","Wu Y","Lowy AM","Alexandrov LB","Riahi I","Xu Q","Zhu F","Skowronska-Krawczyk D","Duran A","Li N","Scott DA","Nicoletti C","Diaz-Meco MT","Morgan T","Todoric J","Watari K","Xian H","Sears RC","Antonucci L","Vucic EA","Karin M"],"additional_accession":[]},"is_claimable":false,"name":"Self-amplifying NRF2-EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer.","description":"Pancreatic ductal adenocarcinoma (PDAC) emerges from mutant KRAS-harboring but dormant low-grade pancreatic intraepithelial neoplasia (PanIN). To examine the role of oxidative stress, a putative PDAC risk factor, we established an organoid-based transformation system. Although the prototypic oxidant H<sub>2</sub>O<sub>2</sub> induced organoid transformation, its effect was nonmutational and was mediated by the oxidant-responsive transcription factor NRF2, which induced the histone methyltransferase EZH2. Congruently, nonoxidizing NRF2 activators triggered organoid malignant conversion through NRF2 and EZH2, establishing a hitherto unknown epigenetic mechanism underlying PanIN-to-PDAC progression. While NRF2 induced EZH2 gene transcription in mouse and human PDAC, EZH2, a general repressor,","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-04-13T08:17:40.306Z","creation":"2026-04-07T13:29:35.016Z"},"accession":"S-EPMC12331375","cross_references":{"pubmed":["40588523"],"doi":["10.1038/s43018-025-01003-3"]}}