Inflammasomes in Colitis and Colorectal Cancer: Mechanism of Action and Therapies

Abstract

Colorectal cancer is a multifactorial disease and a leading cause of cancer-related deaths worldwide. Inflammation is a driver across multiple stages in the development of colorectal cancer. The inflammasome is a cytosolic multiprotein complex of the innate immune system central to the regulation of inflammation, pyroptosis, and other cellular processes important for maintaining gut homeostasis. Studies using mouse models of colitis and colitis-associated colorectal cancer have highlighted diverse and sometimes contrasting roles of inflammasomes in maintaining a balance between intestinal barrier function and the gut microbiota. In addition, persistent and/or dysregulated stimulation of inflammasome sensors finetune inflammation and tumorigenesis in the intestine. This review highlights the emerging role of inflammasome signaling in colitis and colitis-associated colorectal cancer. We also review the key mechanisms by which inflammasome signaling modulate inflammation and tumor development. Finally, we speculate the importance of using more tightly regulated experimental approaches to examine the role of gut microbiota in colorectal cancer.A.P. and C.S. are supported by a John Curtin School of Medical Research International Ph.D. scholarship. S.M.M. is supported by the Australian National University, The Gretel and Gordon Bootes Medical Research Foundation, and the National Health and Medical Research Council of Australia under Project Grants (APP1141504, APP1146864, APP1162103, and APP1163358) and the R.D. Wright Career Development Fellowship (APP1162025). The authors apologize to researchers whose work was not cited or cited through reviews owing to space limitation