NOD-like Receptors: master regulators of inflammation and cancer Mansi Saxena1 & Garabet Yeretssian1,2¶ 1Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA 2Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA ¶ Correspondence to: Garabet Yeretssian, PhD Department of Medicine, Clinical Immunology, Immunology Institute, Tisch Cancer Institute Icahn School of Medicine at Mount Sinai 1425 Madison Avenue, 12-20E New York, NY 10029, USA Tel: (212) 659-9391; (212) 659-9269 Fax: (212) 849-2525 E-mail:
[email protected] 1 ABSTRACT Cytosolic NOD-like receptors (NLRs) have been associated with human diseases including infections, cancer, and autoimmune and inflammatory disorders. These innate immune pattern recognition molecules are essential for controlling inflammatory mechanisms through induction of cytokines, chemokines and antimicrobial genes. Upon activation, some NLRs form multi- protein complexes called inflammasomes, while others orchestrate caspase-independent Nuclear factor kappa B (NF-κB) and Mitogen activated protein kinase (MAPK) signaling. Moreover, NLRs and their downstream signaling components engage in an intricate crosstalk with cell death and autophagy pathways, both critical processes for cancer development. Recently, increasing evidence has extended the concept that chronic inflammation caused by abberant NLR signaling is a powerful driver of carcinogenesis, where it abets genetic mutations, tumor growth and progression. In this review, we explore the rapidly expanding area of research regarding the expression and functions of NLRs in different types of cancers. Furthermore, we particularly focus on how maintaining tissue homeostasis and regulating tissue repair may provide a logical platform for understanding the liaisons between the NLR-driven inflammatory responses and cancer.