期刊
ONCOGENE
卷 37, 期 10, 页码 1340-1353出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41388-017-0038-6
关键词
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资金
- National Medical Research Council, Singapore [NMRC/BNIG/2041/2015, NMRC/CBRG/0044/2013, NMRC/CSA-INV/011/2016, NMRC/CIRG/1434/2015]
- Inter- disciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg
Treatment failure in solid tumors occurs due to the survival of specific subpopulations of cells that possess tumor-initiating (TIC) phenotypes. Studies have implicated G protein-coupled-receptors (GPCRs) in cancer progression and the acquisition of TIC phenotypes. Many of the implicated GPCRs signal through the G protein GNA13. In this study, we demonstrate that GNA13 is upregulated in many solid tumors and impacts survival and metastases in patients. GNA13 levels modulate drug resistance and TIC-like phenotypes in patient-derived head and neck squamous cell carcinoma (HNSCC) cells in vitro and in vivo. Blockade of GNA13 expression, or of select downstream pathways, using small-molecule inhibitors abrogates GNA13-induced TIC phenotypes, rendering cells vulnerable to standard-of-care cytotoxic therapies. Taken together, these data indicate that GNA13 expression is a potential prognostic biomarker for tumor progression, and that interfering with GNA13-induced signaling provides a novel strategy to block TICs and drug resistance in HNSCCs.
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