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首页> 外文期刊>Oncogene >GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers.
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GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers.

机译:在鳞状细胞癌中,GNA13表达促进耐药性和肿瘤起始表型。

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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.
机译:实体肿瘤的治疗失败是由于具有肿瘤起始(TIC)表型的特定亚细胞存活所致。研究表明G蛋白偶联受体(GPCR)参与了癌症的发展和TIC表型的获得。许多牵连的GPCR通过G蛋白GNA13发出信号。在这项研究中,我们证明GNA13在许多实体瘤中上调,并影响患者的生存和转移。 GNA13水平在体外和体内调节患者来源的头颈部鳞状细胞癌(HNSCC)细胞中的耐药性和TIC样表型。使用小分子抑制剂阻断GNA13的表达或某些下游通路的表达,可以消除GNA13诱导的TIC表型,使细胞容易受到标准的细胞毒性治疗。综上所述,这些数据表明GNA13表达是肿瘤进展的潜在预后生物标志物,并且干扰GNA13诱导的信号传导提供了一种在HNSCC中阻断TIC和耐药性的新策略。

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