Inflammation-driven carcinogenesis is mediated through STING.

ABSTRACT: Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by mechanisms that are not well understood. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), cisplatin and etoposide induce nuclear DNA leakage into the cytosol that intrinsically activates stimulator of interferon genes (STING)-dependent cytokine production. Inflammatory cytokine levels are subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING(-/-) mice, or wild-type mice adoptively transferred with STING(-/-) bone marrow, are almost completely resistant to DMBA-induced skin carcinogenesis compared with their wild-type counterparts. Our data establish a r

SUBMITTER: Ahn J 

PROVIDER: S-EPMC4998973 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature