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Title: cGAS–STING cytosolic DNA sensing pathway is suppressed by JAK2-STAT3 in tumor cells
Authors: Suter, Manuel Adrian 
Tan, Nikki Y. 
Thiam, Chung Hwee 
Khatoo, Muznah 
MacAry, Paul A. 
Angeli, Veronique 
Gasser, Stephan 
Zhang, Y. L. 
Issue Date: 31-Mar-2021
Publisher: Nature Research
Citation: Suter, Manuel Adrian, Tan, Nikki Y., Thiam, Chung Hwee, Khatoo, Muznah, MacAry, Paul A., Angeli, Veronique, Gasser, Stephan, Zhang, Y. L. (2021-03-31). cGAS–STING cytosolic DNA sensing pathway is suppressed by JAK2-STAT3 in tumor cells. Scientific Reports 11 (1) : 7243. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Deficiencies in DNA repair and DNA degrading nucleases lead to accumulation of cytosolic DNA. cGAS is a critical DNA sensor for the detection of cytosolic DNA and subsequent activation of the STING signaling pathway. Here, we show that the cGAS-STING pathway was unresponsive to STING agonists and failed to induce type I interferon (IFN) expression in many tested human tumor cells including DU145 prostate cancer cells. Inhibition of IL-6 or the downstream JAK2/STAT3 signaling restored responsiveness to STING agonists in DU145 cells. STING activity in murine TRAMP-C2 prostate cancer cells was critical for tumor rejection and immune cell infiltration. Endogenous STING agonists including double-stranded DNA and RNA:DNA hybrids present in TRAMP-C2 cells contribute to tumor rejection, but tumor growth was further suppressed by administration of cGAMP. Intratumoral co-injections of IL-6 significantly reduced the anti-tumor effects of cGAMP. In summary, STING in tumor cells contributes to tumor rejection in prostate cancer cells, but its functions are frequently suppressed in tumor cells in part via JAK2 and STAT3 pathways. © 2021, The Author(s).
Source Title: Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-021-86644-x
Rights: Attribution 4.0 International
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