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Title: EMT-Induced Stemness and Tumorigenicity Are Fueled by the EGFR/Ras Pathway
Authors: Voon, D.C.-C. 
Wang, H.
Koo, J.K.W. 
Chai, J.H.
Hor, Y.T.
Tan, T.Z.
Chu, Y.-S.
Mori, S.
Ito, Y.
Issue Date: 12-Aug-2013
Citation: Voon, D.C.-C., Wang, H., Koo, J.K.W., Chai, J.H., Hor, Y.T., Tan, T.Z., Chu, Y.-S., Mori, S., Ito, Y. (2013-08-12). EMT-Induced Stemness and Tumorigenicity Are Fueled by the EGFR/Ras Pathway. PLoS ONE 8 (8) : -. ScholarBank@NUS Repository.
Abstract: Recent studies have revealed that differentiated epithelial cells would acquire stem cell-like and tumorigenic properties following an Epithelial-Mesenchymal Transition (EMT). However, the signaling pathways that participate in this novel mechanism of tumorigenesis have not been fully characterized. In Runx3-/-p53-/- murine gastric epithelial (GIF-14) cells, EMT-induced plasticity is reflected in the expression of the embryonal proto-oncogene Hmga2 and Lgr5, an exclusive gastrointestinal stem cell marker. Here, we report the concurrent activation of an EGFR/Ras gene expression signature during TGF-β1-induced EMT in GIF-14 cells. Amongst the altered genes was the induction of Egfr, which corresponded with a delayed sensitization to EGF treatment in GIF-14. Co-treatment with TGF-β1 and EGF or the expression of exogenous KRas led to increased Hmga2 or Lgr5 expression, sphere initiation and colony formation in soft agar assay. Interestingly, the gain in cellular plasticity/tumorigenicity was not accompanied by increased EMT. This uncoupling of EMT and the induction of plasticity reveals an involvement of distinct signaling cues, whereby the EGFR/Ras pathway specifically promotes stemness and tumorigenicity in EMT-altered GIF-14 cells. These data show that the EGFR/Ras pathway requisite for the sustenance of gastric stem cells in vivo and in vitro is involved in the genesis and promotion of EMT-induced tumor-initiating cells. © 2013 Voon et al.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0070427
Appears in Collections:Staff Publications

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