Please use this identifier to cite or link to this item: https://doi.org/10.1002/stem.1183
Title: Runx3 protects gastric epithelial cells against epithelial-mesenchymal transition-induced cellular plasticity and tumorigenicity
Authors: Voon, D.C.-C. 
Wang, H.
Koo, J.K.W. 
Nguyen, T.A.P.
Hor, Y.T.
Chu, Y.-S.
Ito, K.
Fukamachi, H.
Chan, S.L. 
Thiery, J.P.
Ito, Y.
Keywords: Epithelial-mesenchymal transition
Gastric cancer stem cell
Lgr5
RUNX3
TGF-β
Wnt
Issue Date: Oct-2012
Citation: Voon, D.C.-C., Wang, H., Koo, J.K.W., Nguyen, T.A.P., Hor, Y.T., Chu, Y.-S., Ito, K., Fukamachi, H., Chan, S.L., Thiery, J.P., Ito, Y. (2012-10). Runx3 protects gastric epithelial cells against epithelial-mesenchymal transition-induced cellular plasticity and tumorigenicity. Stem Cells 30 (10) : 2088-2099. ScholarBank@NUS Repository. https://doi.org/10.1002/stem.1183
Abstract: The transcription factor RUNX3 functions as a tumor suppressor in the gastrointestinal epithelium, where its loss is an early event in carcinogenesis. While RUNX3 acts concurrently as a mediator of TGF-β signaling and an antagonist of Wnt, the cellular changes that follow its loss and their contribution to tumorigenicity are not fully understood. Here, we report that the loss of Runx3 in gastric epithelial cells results in spontaneous epithelial-mesenchymal transition (EMT). This produces a tumorigenic stem cell-like subpopulation, which remarkably expresses the gastric stem cell marker Lgr5. This phenomenon is due to the compounding effects of the dysregulation of the TGF-β and Wnt pathways. Specifically, Runx3-/-p53 -/- gastric epithelial cells were unexpectedly sensitized for TGF-β-induced EMT, during which the resultant induction of Lgr5 was enhanced by an aberrantly activated Wnt pathway. These data demonstrate a protective role for RUNX3 in safeguarding gastric epithelial cells against aberrant growth factor signaling and the resultant cellular plasticity and stemness. © AlphaMed Press.
Source Title: Stem Cells
URI: http://scholarbank.nus.edu.sg/handle/10635/115277
ISSN: 10665099
DOI: 10.1002/stem.1183
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