TTK激活Akt并促进肝癌细胞的增殖和迁移。

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

作者信息

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

机构信息

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.

出版信息

Oncotarget. 2015 Oct 27;6(33):34309-20. doi: 10.18632/oncotarget.5295.

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.

肝细胞癌（HCC）是临床预后较差的最恶性癌症之一。蛋白激酶人单极纺锤体1（hMps1/TTK）基因在肝癌中表达显著增加。然而，其在肝癌发生中的作用仍不清楚。在本研究中，我们发现TTK在77.63%（118/152）的肝癌标本中过表达。TTK表达升高与肿瘤体积大及门静脉癌栓（PVTT）的存在呈正相关。其启动子去甲基化增加了肝癌中TTK的表达。体外实验表明，TTK不仅促进细胞增殖和非锚定依赖性生长，还促进细胞迁移。随后的研究表明，TTK以p53依赖的方式激活Akt/mTOR通路。我们还发现TTK特异性激酶抑制剂AZ3146可降低肝癌细胞生长。总之，TTK通过促进细胞增殖和迁移促进肝癌发生。它可能作为一种新的生物标志物和肝癌治疗的潜在靶点。