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极光激酶A(AURKA)通过调控AURKA/蛋白激酶B(Akt)/粘着斑激酶(FAK)信号通路促进头颈部鳞状细胞癌的细胞迁移和侵袭。

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway.

作者信息

Wu Jichang, Yang Liyun, Shan Yamin, Cai Changping, Wang Shili, Zhang Hao

机构信息

Department of Otolaryngology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, P.R. China.

出版信息

Oncol Lett. 2016 Mar;11(3):1889-1894. doi: 10.3892/ol.2016.4110. Epub 2016 Jan 14.

Abstract

The present study aimed to investigate the mechanism by which Aurora kinase A (AURKA) promotes cell migration and invasion in head and neck squamous cell carcinoma (HNSCC). Transwell assays were performed to investigate the cell migration and invasion abilities of AURKA, whilst western blotting was used to analyze the protein expression in FaDu and Hep2 cells, each treated with pharmacological inhibitors. Following the inhibition of AURKA, Akt and focal adhesion kinase (FAK), the migration and invasion of the FaDu and Hep2 cells decreased. The expression of phosphorylated (p)-AURKA and p-FAK (Y397) was observed to decrease following FaDu and Hep2 cell treatment with VX-680, a small molecular inhibitor of AURKA. The expression of p-Akt and p-FAK (Y397) ceased following treatment with the Akt inhibitor triciribine. The expression of p-FAK (Y397) decreased, however, p-Akt expression did not change following treatment with the FAK inhibitor TAE226. In conclusion, AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC.

摘要

本研究旨在探究极光激酶A(AURKA)促进头颈部鳞状细胞癌(HNSCC)细胞迁移和侵袭的机制。进行Transwell实验以研究AURKA的细胞迁移和侵袭能力,同时使用蛋白质免疫印迹法分析用药物抑制剂处理后的FaDu和Hep2细胞中的蛋白质表达。抑制AURKA、Akt和粘着斑激酶(FAK)后,FaDu和Hep2细胞的迁移和侵袭能力降低。在用AURKA的小分子抑制剂VX - 680处理FaDu和Hep2细胞后,观察到磷酸化(p)-AURKA和p-FAK(Y397)的表达降低。在用Akt抑制剂曲西立滨处理后,p-Akt和p-FAK(Y397)的表达停止。在用FAK抑制剂TAE226处理后,p-FAK(Y397)的表达降低,然而p-Akt的表达没有变化。总之,AURKA通过AURKA/Akt/FAK信号通路激活FAK,促进HNSCC细胞的迁移和侵袭,这可能随后为HNSCC的治疗提供一种新方法。

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