title: Cutting edge: STING mediates protection against colorectal tumorigenesis by governing the magnitude of intestinal inflammation.
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.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163;
authors.forename: Qifan
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105;
authors.forename: Si Ming
authors.initials: SM
authors.lastname: Man
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105;
authors.forename: Prajwal
authors.initials: P
authors.lastname: Gurung
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105;
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, TN 38105;
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.affiliation: Department of Medical Protein Research, Flemish Institute for Biotechnology, B-9000 Ghent, Belgium; and Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lamkanfi
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; Thirumala-Devi.Kanneganti@StJude.org.
authors.forename: Thirumala-Devi
authors.initials: TD
authors.lastname: Kanneganti
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D000099197:STING Protein
chemical_list: D054360:Chemokine CXCL1; D015850:Interleukin-6; D008565:Membrane Proteins; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C475895:Cxcl1 protein, mouse; C494087:Stat3 protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein