title: TTK activates Akt and promotes proliferation and migration of hepatocellular carcinoma cells.
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.
authors.affiliation: National Engineering Center for Biochip at Shanghai, Shanghai, China.|Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Hepatology Institute of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Liao
authors.affiliation: National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ou
authors.affiliation: National Engineering Center for Biochip at Shanghai, Shanghai, China.|Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China.|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.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D019175:DNA Methylation / Q000502:physiology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C075840:TTK protein, human
keywords: Akt; TTK gene; cell migration; demethylation; hepatocarcinogenesis