| First Author | Ahn J | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 5166 | PubMed ID | 25300616 |
| Mgi Jnum | J:225338 | Mgi Id | MGI:5692402 |
| Doi | 10.1038/ncomms6166 | Citation | Ahn J, et al. (2014) Inflammation-driven carcinogenesis is mediated through STING. Nat Commun 5:5166 |
| abstractText | 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. |
