| Autor: |
Lee J; Department of Medicine, University of California at San Diego, La Jolla, California 92093-0663, USA. j142lee@ucsd.edu, Kim JC, Lee SE, Quinley C, Kim H, Herdman S, Corr M, Raz E |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2012 May 25; Vol. 287 (22), pp. 18182-9. Date of Electronic Publication: 2012 Apr 10. |
| DOI: |
10.1074/jbc.M111.328831 |
| Abstrakt: |
STAT3 was recently reported to suppress tumor invasion in Apc(min)(/+) mice. We investigated the mechanisms by which STAT3 inhibits intestinal epithelial tumors using Apc(min)(/+)/Stat3(IEC-KO) mice (intestinal epithelial cell (IEC)-specific deletion of STAT3 in the Apc(min)(/+) background) to determine the role of STAT3 in carcinogenesis in vivo as well as colorectal cancer cell lines in vitro. To inhibit invasion of IEC tumors, STAT3 functions as a molecular adaptor rather than a transcription factor. Accordingly, the tumors in Apc(min)(/+)/Stat3(IEC-KO) mice undergo adenoma-to-carcinoma transition and acquire an invasive phenotype. Similarly, STAT3 knockdown in a colorectal cell line enhances IEC invasion. We demonstrate that STAT3 down-regulates SNAI (Snail-1) expression levels and hence suppresses epithelial-mesenchymal transition of colorectal cancer cells. Mechanistically, STAT3 facilitates glycogen synthase kinase (GSK) 3β-mediated degradation of SNAI by regulating phosphorylation of GSK3β. Our data identified a new role for STAT3 in the adenoma-to-carcinoma sequence of intestinal tumors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
