Diverging inflammasome signals in tumorigenesis and potential targeting

Abstract

Inflammasomes are molecular platforms that assemble upon sensing various intracellular stimuli. Inflammasome assembly leads to activation of caspase-1, thereby promoting the secretion of bioactive interleukin-1β and interleukin-18 and inducing an inflammatory cell death called pyroptosis. Effectors of the inflammasome efficiently drive an immune response, primarily providing protection against microbial infections and mediating control over sterile insults. However, aberrant inflammasome signaling is associated with pathogenesis of inflammatory and metabolic diseases, neurodegeneration, and malignancies. Chronic inflammation perpetuated by inflammasome activation plays a central role in all stages of tumorigenesis, including immunosuppression, proliferation, angiogenesis, and metastasis. Conversely, inflammasome signaling also contributes to tumor suppression by maintaining intestinal barrier integrity, which portrays the diverse roles of inflammasomes in tumorigenesis. Studies have underscored the significance of environmental factors, such as diet and gut microbiota [G] in inflammasome signaling, which in turn influences tumorigenesis. In this review, we deliver an overview of the interplay between inflammasomes and tumorigenesis and discuss their potential as a therapeutic target. Inflammasome signaling in myeloid cells largely protects against microbial infections. Aberrant inflammasome signaling promotes chronic inflammation, which contributes to tumorigenesis. This Review presents an overview of the diverging roles of inflammasomes in cancer and discuss its targeting potential in anti-cancer therapy.