RGD Reference Report - KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs. - Rat Genome Database

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KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs.

Authors: Tzatsos, A  Paskaleva, P  Ferrari, F  Deshpande, V  Stoykova, S  Contino, G  Wong, KK  Lan, F  Trojer, P  Park, PJ  Bardeesy, N 
Citation: Tzatsos A, etal., J Clin Invest. 2013 Feb 1;123(2):727-39. doi: 10.1172/JCI64535. Epub 2013 Jan 16.
RGD ID: 9588253
Pubmed: PMID:23321669   (View Abstract at PubMed)
PMCID: PMC3561797   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI64535   (Journal Full-text)

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 genome-wide gene expression and ChIP studies revealed that KDM2B drives tumorigenicity through 2 different transcriptional mechanisms. KDM2B repressed developmental genes through cobinding with Polycomb group (PcG) proteins at transcriptional start sites, whereas it activated a module of metabolic genes, including mediators of protein synthesis and mitochondrial function, cobound by the MYC oncogene and the histone demethylase KDM5A. These results defined epigenetic programs through which KDM2B subverts cellular differentiation and drives the pathogenesis of an aggressive subset of PDAC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pancreatic ductal carcinoma severityIEP 9588253mRNA and protein:increased expression:pancreas (human)RGD 
pancreatic ductal carcinoma severityISOKDM2B (Homo sapiens)9588253; 9588253mRNA and protein:increased expression:pancreas (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdm2b  (lysine demethylase 2B)

Genes (Mus musculus)
Kdm2b  (lysine (K)-specific demethylase 2B)

Genes (Homo sapiens)
KDM2B  (lysine demethylase 2B)


Additional Information