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IRAK-M Expression in Tumor Cells Supports Colorectal Cancer Progression through Reduction of Antimicrobial Defense and Stabilization of STAT3.
- Source :
-
Cancer Cell . May2016, Vol. 29 Issue 5, p684-696. 13p. - Publication Year :
- 2016
-
Abstract
- Summary Colorectal cancer (CRC) is associated with loss of epithelial barrier integrity, which facilitates the interaction of the immunological microenvironment with the luminal microbiome, eliciting tumor-supportive inflammation. An important regulator of intestinal inflammatory responses is IRAK-M, a negative regulator of TLR signaling. Here we investigate the compartment-specific impact of IRAK-M on colorectal carcinogenesis using a mouse model. We demonstrate that IRAK-M is expressed in tumor cells due to combined TLR and Wnt activation. Tumor cell-intrinsic IRAK-M is responsible for regulation of microbial colonization of tumors and STAT3 protein stability in tumor cells, leading to tumor cell proliferation. IRAK-M expression in human CRCs is associated with poor prognosis. These results suggest that IRAK-M may be a potential therapeutic target for CRC treatment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15356108
- Volume :
- 29
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Cancer Cell
- Publication Type :
- Academic Journal
- Accession number :
- 115218378
- Full Text :
- https://doi.org/10.1016/j.ccell.2016.03.014