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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
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
- Source :
- The Journal of biological chemistry. 287(22)
- Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- Adenoma
STAT3 Transcription Factor
Epithelial-Mesenchymal Transition
Genes, APC
Down-Regulation
medicine.disease_cause
Biochemistry
Polymerase Chain Reaction
Mice
GSK-3
Intestinal Neoplasms
medicine
Animals
Epithelial–mesenchymal transition
RNA, Small Interfering
STAT3
Molecular Biology
Transcription factor
Cell Proliferation
DNA Primers
Mice, Knockout
biology
Base Sequence
Cell growth
Carcinoma
Molecular Bases of Disease
Cell Biology
STAT protein
biology.protein
Cancer research
Snail Family Transcription Factors
Carcinogenesis
Transcription Factors
Subjects
Details
- ISSN :
- 1083351X
- Volume :
- 287
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....37656fd07b9fc7d55bf8b4fe6f2709d0