Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/136750
Title: STING IN TUMOR CELLS IS REQUIRED FOR THE ANTI-CANCER EFFECTS OF STING AGONISTS AND STAT3 INHIBITORS
Authors: ZHANG YALING
Keywords: Innate immunity, Cytosolic DNA, cGAS, STING, Type I IFN, IL-6
Issue Date: 31-May-2017
Source: ZHANG YALING (2017-05-31). STING IN TUMOR CELLS IS REQUIRED FOR THE ANTI-CANCER EFFECTS OF STING AGONISTS AND STAT3 INHIBITORS. ScholarBank@NUS Repository.
Abstract: Deficiencies in DNA repair and DNA degrading nucleases can lead to accumulation of cytosolic DNA and the activation of STING pathways in tumor cells. The DNA sensors that recognize cytosolic DNA in tumor cells are not known. Here we show that double-stranded DNA and RNA:DNA hybrids bind cGAS and activate the cGAS-STING pathway in tumor cells. STING deficiency in murine TRAMP-C2 prostate cancer cells impaired tumor rejection and immune infiltration of the tumor. However, STING dysfunction in many human tumor cells abrogated responsiveness to exogenous STING agonists. The unresponsiveness of STING to agonists was not maintained by cytosolic DNA, cGAS or type I interferons in cancer cells, but depended on autocrine IL-6 in DU145 prostate cancer cells. In summary, we show that tumor rejection depends on recognition of cytosolic DNA by the cGAS-STING pathway, which is frequently suppressed in cancer cells.
URI: http://scholarbank.nus.edu.sg/handle/10635/136750
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