title: 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 role for STING in the control of cancer, shed significant insight into the causes of inflammation-driven carcinogenesis and may provide a basis for therapeutic strategies to help prevent malignant disease.
authors.affiliation: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: Jeonghyun
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: Tianli
authors.initials: T
authors.lastname: Xia
authors.affiliation: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Konno
authors.affiliation: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Konno
authors.affiliation: Department of Surgery, University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.affiliation: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: Glen N
authors.initials: GN
authors.lastname: Barber
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000099197:STING Protein
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; D016207:Cytokines; D005090:Exodeoxyribonucleases; D008565:Membrane Proteins; D010750:Phosphoproteins; C530855:Sting1 protein, mouse; D000099197:STING Protein; C429526:three prime repair exonuclease 1