Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0070427
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dc.titleEMT-Induced Stemness and Tumorigenicity Are Fueled by the EGFR/Ras Pathway
dc.contributor.authorVoon, D.C.-C.
dc.contributor.authorWang, H.
dc.contributor.authorKoo, J.K.W.
dc.contributor.authorChai, J.H.
dc.contributor.authorHor, Y.T.
dc.contributor.authorTan, T.Z.
dc.contributor.authorChu, Y.-S.
dc.contributor.authorMori, S.
dc.contributor.authorIto, Y.
dc.date.accessioned2014-11-26T09:59:38Z
dc.date.available2014-11-26T09:59:38Z
dc.date.issued2013-08-12
dc.identifier.citationVoon, 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. https://doi.org/10.1371/journal.pone.0070427
dc.identifier.issn19326203
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/110736
dc.description.abstractRecent 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.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1371/journal.pone.0070427
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.description.doi10.1371/journal.pone.0070427
dc.description.sourcetitlePLoS ONE
dc.description.volume8
dc.description.issue8
dc.description.page-
dc.description.codenPOLNC
dc.identifier.isiut000323097300017
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