biostudies-literatureTzatsos ANCI NIH HHS727-39https://www.ebi.ac.uk/biostudies/studies/S-EPMC3561797biostudies-literatureUnknown123(2)Epigenetic mechanisms mediate heritable control of cell identity in normal cells and cancer. We sought to identify epigenetic regulators driving the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers. We found that KDM2B (also known as Ndy1, FBXL10, and JHDM1B), an H3K36 histone demethylase implicated in bypass of cellular senescence and somatic cell reprogramming, is markedly overexpressed in human PDAC, with levels increasing with disease grade and stage, and highest expression in metastases. KDM2B silencing abrogated tumorigenicity of PDAC cell lines exhibiting loss of epithelial differentiation, whereas KDM2B overexpression cooperated with KrasG12D to promote PDAC formation in mouse models. Gain- and loss-of-function experiments coupled to genThe Journal of clinical investigationKDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs.PMC35617971 R01 CA133557-01P01 CA117969-06K99 CA158582P50 CA127003R01 CA133557P01 CA117969Deshpande VPark PJLan FTzatsos ABardeesy NFerrari FPaskaleva PContino GWong KKStoykova STrojer PfalseKDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs.Epigenetic mechanisms mediate heritable control of cell identity in normal cells and cancer. We sought to identify epigenetic regulators driving the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers. We found that KDM2B (also known as Ndy1, FBXL10, and JHDM1B), an H3K36 histone demethylase implicated in bypass of cellular senescence and somatic cell reprogramming, is markedly overexpressed in human PDAC, with levels increasing with disease grade and stage, and highest expression in metastases. KDM2B silencing abrogated tumorigenicity of PDAC cell lines exhibiting loss of epithelial differentiation, whereas KDM2B overexpression cooperated with KrasG12D to promote PDAC formation in mouse models. Gain- and loss-of-function experiments coupled to gen2013-01-01T00:00:00Z2013 Feb2026-05-05T17:02:03.394Z2019-03-27T01:04:12ZS-EPMC35617972332166910.1172/jci6453510.1172/JCI64535