Document Detail


Runx3 Protects Gastric Epithelial Cells Against Epithelial- Mesenchymal Transition-Induced Cellular Plasticity and Tumorigenicity.
MedLine Citation:
PMID:  22899304     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Dominic Chih-Cheng Voon; Huajing Wang; Jason Kin Wai Koo; Tu Anh Pham Nguyen; Yit Teng Hor; Yeh-Shiu Chu; Kosei Ito; Hiroshi Fukamachi; Shing Leng Chan; Jean Paul Thiery; Yoshiaki Ito
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-16
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  -     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 AlphaMed Press.
Affiliation:
Cancer Biology Program, Cancer Science Institute Singapore, National University of Singapore, Singapore 1174561.
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