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Front Immunol. 2014 Nov 17;5:553. doi: 10.3389/fimmu.2014.00553. eCollection 2014.

IL-1 Receptor-Associated Kinase Signaling and Its Role in Inflammation, Cancer Progression, and Therapy Resistance.

Author information

1
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, State University of New York Upstate Medical University , Albany, NY , USA.
2
Department of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, MD , USA.
3
Department of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, MD , USA ; Greenebaum Cancer Center , Baltimore, MD , USA.

Abstract

Chronic inflammation has long been associated with the development of cancer. Among the various signaling pathways within cancer cells that can incite the expression of inflammatory molecules are those that activate IL-1 receptor-associated kinases (IRAK). The IRAK family is comprised of four family members, IRAK-1, IRAK-2, IRAK-3 (also known as IRAK-M), and IRAK-4, which play important roles in both positively and negatively regulating the expression of inflammatory molecules. The wide array of inflammatory molecules that are expressed in response to IRAK signaling within the tumor microenvironment regulate the production of factors which promote tumor growth, metastasis, immune suppression, and chemotherapy resistance. Based on published reports we propose that dysregulated activation of the IRAK signaling pathway in cancer cells contributes to disease progression by creating a highly inflammatory tumor environment. In this article, we present both theoretical arguments and reference experimental data in support of this hypothesis.

KEYWORDS:

IRAK-4; cancer; inflammation; therapeutics; toll-like receptors

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