Cutting Edge: STING Mediates Protection against Colorectal Tumorigenesis by Governing the Magnitude of Intestinal Inflammation
Year: 2014
Type: article
Abstract: Stimulator of IFN genes (STING) is a cytoplasmic innate immune sensor for cyclic dinucleotides that also serves a dual role as an adaptor molecule for a number of intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and autoimmune diseases, its physiological role in cancer is unknown. In this study, we show that STING-deficient mice are highly susceptible to colitis-associated colorectal cancer. Colons of STING-deficient mice exhibit significant intestinal damage and overt proliferation during early stages of tumorigenesis. Moreover, STING-deficient mice fail to restrict activation of the NF-κB- and STAT3-signaling pathways, which leads to increased levels of the proinflammatory cytokines IL-6 and KC. Therefore, our results identified an unexpected and important role for STING in mediating protection against colorectal tumorigenesis.
Source: The Journal of Immunology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: St. Jude Children's Research Hospital, American Lebanese Syrian Associated Charities, European Commission, Vlaamse regering, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, FP7 Ideas: European Research Council
Awards: G137859075, Signaling and activation pathways of the NOD-like receptors Ipaf, Nlrp1b and Nlrp12, Role of IL-1alpha signaling in inflammatory diseases and host defense, G2851941416, G3789341260, G3831755428, G4533544333, Role of caspase-11 in inflammasome signaling and the innate immune response, G5372223083, Inflammatory Caspases in Innate Immunity and Inflammation, G8167955467, Inflammatory Caspases in Innate Immunity and Inflammation, Cancer Center Support Grant (CCSG)
OpenAlex ID: W2160026601