TTK activates Akt and promotes proliferation and migration of hepatocellular carcinoma cells

// Xing Liu 1, 2 , Weijia Liao 4 , Qing Yuan 1 , Ying Ou 1 , Jian Huang 1, 2, 3 1 National Engineering Center for Biochip at Shanghai, Shanghai, China 2 Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China 3 Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China 4 Hepatology Institute of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China Correspondence to: Jian Huang, e-mail: huangjchgc@hotmail.com Xing Liu, e-mail: liuxing118@aliyun.com Keywords: hepatocarcinogenesis, TTK gene, cell migration, demethylation, Akt Received: April 19, 2015 Accepted: September 07, 2015 Published: September 19, 2015 ABSTRACT Hepatocellular carcinoma (HCC) is one of the most malignant cancers with poor clinical outcome. The protein kinase human monopolar spindle 1 (hMps1/TTK) gene expression is significantly increased in HCCs. However, its contributions to hepatocarcinogenesis remain unclear. In this study, we found that TTK was overexpressed in 77.63% (118/152) HCC specimens. Elevated TTK expression positively correlated with large tumor size and presence of the portal vein tumor thrombus (PVTT). Demethylation in its promoter increased TTK expression in HCC. In vitro assays revealed that TTK not only promoted cell proliferation and anchorage-independent growth, but also cell migration. Subsequent investigations revealed that TTK activated Akt/mTOR pathway in a p53 dependent manner. We also found that TTK specific kinase inhibitor AZ3146 could decrease HCC cell growth. In conclusion, TTK contributes to HCC tumorigenesis via promoting cell proliferation and migration. It may serve as a novel biomarker and a potential target in HCC cancer therapy.