IRAK-M Expression in Tumor Cells Supports Colorectal Cancer Progression through Reduction of Antimicrobial Defense and Stabilization of STAT3

Kesselring R, Glaesner J, Hiergeist A, Naschberger E, Neumann H, Brunner SM, Wege AK, Seebauer C, Koehl G, Merkl S, Croner RS, Hackl C, Stürzl M, Neurath M, Gessner A, Schlitt HJ, Geissler EK, Fichtner-Feigl S (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Cancer Cell Elsevier (Cell Press)

Book Volume: 29

Pages Range: 684-96

Journal Issue: 5

DOI: 10.1016/j.ccell.2016.03.014

Abstract

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.

Authors with CRIS profile

Elisabeth Naschberger Medizinische Fakultät Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1)

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE) Universität Regensburg DE Germany (DE)

How to cite

APA:

Kesselring, R., Glaesner, J., Hiergeist, A., Naschberger, E., Neumann, H., Brunner, S.M.,... Fichtner-Feigl, S. (2016). IRAK-M Expression in Tumor Cells Supports Colorectal Cancer Progression through Reduction of Antimicrobial Defense and Stabilization of STAT3. Cancer Cell, 29(5), 684-96. https://doi.org/10.1016/j.ccell.2016.03.014

MLA:

Kesselring, Rebecca, et al. "IRAK-M Expression in Tumor Cells Supports Colorectal Cancer Progression through Reduction of Antimicrobial Defense and Stabilization of STAT3." Cancer Cell 29.5 (2016): 684-96.

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