Please use this identifier to cite or link to this item:
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
Source: 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

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
2013-emt-induced_stemness_tumorigenicity_fueled_EGFR-published.pdf865.56 kBAdobe PDF




checked on Feb 28, 2018


checked on Feb 21, 2018

Page view(s)

checked on Feb 27, 2018


checked on Feb 27, 2018

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.