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- W4376132324 abstract "Cyclic GMP-AMP synthase (cGAS) is a DNA sensor and responsible for inducing an antitumor immune response. Recent studies reveal that cGAS is frequently inhibited in cancer, and therapeutic targets to promote antitumor cGAS function remain elusive. SRC is a proto-oncogene tyrosine kinase and is expressed at elevated levels in numerous cancers. Here, we demonstrate that SRC expression in primary and metastatic bladder cancer negatively correlates with innate immune gene expression and immune cell infiltration. We determine that SRC restricts cGAS signaling in human cell lines through SRC small molecule inhibitors, depletion, and overexpression. cGAS and SRC interact in cells and in vitro, while SRC directly inhibits cGAS enzymatic activity and DNA binding in a kinase-dependent manner. SRC phosphorylates cGAS, and inhibition of cGAS Y248 phosphorylation partially reduces SRC inhibition. Collectively, our study demonstrates that cGAS antitumor signaling is hindered by the proto-oncogene SRC and describes how cancer-associated proteins can regulate the innate immune system." @default.
- W4376132324 created "2023-05-12" @default.
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- W4376132324 date "2023-06-22" @default.
- W4376132324 modified "2023-09-27" @default.
- W4376132324 title "The proto-oncogene SRC phosphorylates cGAS to inhibit an antitumor immune response" @default.
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- W4376132324 doi "https://doi.org/10.1172/jci.insight.167270" @default.
- W4376132324 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37166992" @default.
- W4376132324 hasPublicationYear "2023" @default.
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