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EpCAM regulates cell cycle progression via control of cyclin D1 expression.
Oncogene 32, 641-650 (2013)
The epithelial cell adhesion molecule (EpCAM) is an integral transmembrane protein that is frequently overexpressed in embryonic stem cells, tissue progenitors, carcinomas and cancer-initiating cells. In cancer cells, expression of EpCAM is associated with enhanced proliferation and upregulation of target genes including c-myc. However, the exact molecular mechanisms underlying the observed EpCAM-dependent cell proliferation remained unexplored. Here, we show that EpCAM directly affects cell cycle progression via its capacity to regulate the expression of cyclin D1 at the transcriptional level and depending on the direct interaction partner FHL2 (four-and-a-half LIM domains protein 2). As a result, downstream events such as phosphorylation of the retinoblastoma protein (Rb) and expression of cyclins E and A are similarly affected. In vivo, EpCAM expression strength and pattern are both positively correlated with the proliferation marker Ki67, high expression and nuclear localisation of cyclin D1, and Rb phosphorylation. Thus, EpCAM enhances cell cycle progression via the classical cyclin-regulated pathway.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Epcam ; Epicd ; Cyclin D1; Epithelial Ovarian-cancer ; Embryonic Stem-cells ; Ep-cam ; Hepatocellular-carcinoma ; Breast-cancer ; Potential Target ; Gene-expression ; Antigen Epcam ; Beta-catenin ; Fhl2
ISSN (print) / ISBN 0950-9232
Quellenangaben Volume: 32, Issue: 5, Pages: 641-650
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)