title: Diverse roles of STING-dependent signaling on the development of cancer.
abstract: Stimulator of interferon genes (STING) is a cellular sensor that controls cytosolic DNA-activated innate immune signaling. We have previously demonstrated that STING-deficient mice are resistant to carcinogen-induced skin cancer, similar to myeloid differentiation primary response gene 88 (MyD88) deficient mice, since the production of STING-dependent DNA-damage-induced proinflammatory cytokines, that likely require MyD88 signaling to exert their growth-promoting activity, are prevented. In contrast, MyD88-deficient mice are sensitive to colitis-associated cancer (CAC), since selected cytokines generated following DNA-damage also activate repair pathways, which can help prevent tumor development. Here, we demonstrate that STING signaling facilitates wound repair processes and that analogous to MyD88-deficient mice, STING-deficient mice (SKO) are prone to CAC induced by DNA-damaging agents. SKO mice harboring tumors exhibited low levels of tumor-suppressive interleukin-22 binding protein (IL-22BP) compared to normal mice, a cytokine considered critical for preventing colon-related cancer. Our data indicate that STING constitutes a critical component of the host early response to intestinal damage and is essential for invigorating tissue repair pathways that may help prevent tumorigenesis.
authors: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA.
authors: J
authors: J
authors: Ahn
authors: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA.
authors: H
authors: H
authors: Konno
authors: Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA.
authors: G N
authors: GN
authors: Barber
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000494:pharmacology; D063646:Carcinogenesis / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000187:drug effects; D000099197:STING Protein
chemical_list: D001397:Azoxymethane; D008565:Membrane Proteins; C532857:STING1 protein, human; D000099197:STING Protein
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