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Diverse roles of STING-dependent signaling on the development of cancer

Oncogene volume 34, pages 5302–5308 (2015)Cite this article

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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.

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Acknowledgements

We thank Dr Masayuki Fukata for micro-endoscopy analysis; Ms Delia Gutman and Ms Auristela Rivera for mice breeding; Dr Tianli Xia for helping with confocal analysis; Dr Biju Issac of the Sylvester Comprehensive Cancer Center Bioinformatics Core Facility for Gene expression array analysis; Dr Phillp Ruiz and Ms Dayami Hernandez for helping with immunohistochemistry.

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  1. Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA

    J Ahn, H Konno & G N Barber

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  1. J Ahn
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  2. H Konno
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  3. G N Barber
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Correspondence to G N Barber.

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Ahn, J., Konno, H. & Barber, G. Diverse roles of STING-dependent signaling on the development of cancer. Oncogene 34, 5302–5308 (2015). https://doi.org/10.1038/onc.2014.457

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