IRAK-M Expression in Tumor Cells Supports Colorectal Cancer Progression through Reduction of Antimicrobial Defense and Stabilization of STAT3
| Autor: | Joachim Glaesner, Elisabeth Naschberger, Christina Hackl, Andreas Hiergeist, Stefan Fichtner-Feigl, Rebecca Kesselring, André Gessner, Susanne Merkl, Michael Stürzl, Caroline Theresa Seebauer, Markus F. Neurath, Gudrun Köhl, HJ Schlitt, Roland S. Croner, Anja K. Wege, Stefan M. Brunner, Helmut Neumann, Edward K. Geissler |
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| Rok vydání: | 2016 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Cancer Research Colorectal cancer Immunoblotting Regulator Mice Nude Inflammation Mouse model of colorectal and intestinal cancer Biology 03 medical and health sciences medicine Animals Humans Microbiome Phosphorylation STAT3 Wnt Signaling Pathway Cell Proliferation Mice Knockout Protein Stability Cell growth Microbiota Toll-Like Receptors Wnt signaling pathway Cell Biology Colitis Prognosis medicine.disease Immunohistochemistry Survival Analysis Mice Inbred C57BL Interleukin-1 Receptor-Associated Kinases 030104 developmental biology Oncology Host-Pathogen Interactions Immunology Disease Progression biology.protein medicine.symptom Colorectal Neoplasms |
| Zdroj: | Cancer Cell. 29:684-696 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccell.2016.03.014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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