| First Author | Lee J | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 22 | Pages | 18182-9 |
| PubMed ID | 22496368 | Mgi Jnum | J:185613 |
| Mgi Id | MGI:5429481 | Doi | 10.1074/jbc.M111.328831 |
| Citation | Lee J, et al. (2012) Signal transducer and activator of transcription 3 (STAT3) protein suppresses adenoma-to-carcinoma transition in Apcmin/+ mice via regulation of Snail-1 (SNAI) protein stability. J Biol Chem 287(22):18182-9 |
| abstractText | 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) 3beta-mediated degradation of SNAI by regulating phosphorylation of GSK3beta. Our data identified a new role for STAT3 in the adenoma-to-carcinoma sequence of intestinal tumors. |
