Suppression of Antimicrobial Defense and Stabilization of STAT3 by IRAK-M Expression in Tumor Cells Promotes Colorectal Carcinogenesis

Irshad Ali; Young-Sang Koh

doi:10.4167/jbv.2016.46.3.181

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Ali and Koh: Suppression of Antimicrobial Defense and Stabilization of STAT3 by IRAK-M Expression in Tumor Cells Promotes Colorectal Carcinogenesis

Research Update (Minireview)

J Bacteriol Virol 2016;46(3):181-183.

Published online: 9 February 2016

DOI: https://doi.org/10.4167/jbv.2016.46.3.181

Suppression of Antimicrobial Defense and Stabilization of STAT3 by IRAK-M Expression in Tumor Cells Promotes Colorectal Carcinogenesis

Irshad Ali, Young-Sang Koh^∗

Department of Microbiology and Immunology, School of Medicine and Brain Korea 21 PLUS Program, and Institute of Medical Science, Jeju National University, Jeju, Korea

^∗Corresponding author: Young-Sang Koh. Department of Microbiology and Immunology, Jeju National University School of Medicine, 102 Jejudaehakno, Jeju 63243, Korea. Phone: +82-64-754-3851, Fax: +82-64-702-2687, e-mail: yskoh7@jejunu.ac.kr

^∗∗ This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1120340).

Received 24 June 20164 July 2016 Accepted 5 July 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Different environmental and genetic factors have been attributed to the etiology of colorectal cancer. Dysbiotic gut microbiota is associated with initiation and progression of colon carcinogenesis. Hyperactivation of STAT3 promotes carcinogenesis by upregulating cell proliferation, survival, tumor-induced immunosupression and angiogenesis. IRAK-M is a negative regulator of toll-like receptor signaling and inhibits innate immune response. The cancer cell may exploit this property of IRAK-M and evade host immune surveillance. Recently, it has been found that IRAK-M provide controlled feed back to bacteria involved in colorectal cancer by reducing antibacterial response in mice. Furthermore, IRAK-M increased the stability of STAT3 in tumor cells that support tumor promotion by upregulating cell proliferation and survival. Thus, it is suggested that IRAK-M promotes colitis associated colon cancer by enhancing bacterial colonization and stabilization of STAT3.

Keywords: IRAK-M, Microbiota, STAT3, Colon cancer

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