Oncotarget

Research Papers:

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

Xing Liu _, Weijia Liao, Qing Yuan, Ying Ou and Jian Huang

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Oncotarget. 2015; 6:34309-34320. https://doi.org/10.18632/oncotarget.5295

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Abstract

Xing Liu1,2, Weijia Liao4, Qing Yuan1, Ying Ou1, Jian Huang1,2,3

1National Engineering Center for Biochip at Shanghai, Shanghai, China

2Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China

3Key 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

4Hepatology Institute of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China

Correspondence to:

Jian Huang, e-mail: [email protected]

Xing Liu, e-mail: [email protected]

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.


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