TTK activates Akt and promotes proliferation and migration of hepatocellular carcinoma cells.
TTK activates Akt and promotes proliferation and migration of hepatocellular carcinoma cells.
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TTK激活Akt促进肝癌细胞增殖和迁移
DOI：
10.18632/oncotarget.5295
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发表时间：
2015-10-27
期刊：
影响因子：
--
通讯作者：
Huang J
中科院分区：
文献类型：
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作者：
Liu X;Liao W;Yuan Q;Ou Y;Huang J
肝细胞癌（HCC）是最恶性的癌症之一，临床结果较差。 HCC 中蛋白激酶人单极纺锤体 1 (hMps1/TTK) 基因表达显着增加。然而，其对肝癌发生的贡献仍不清楚。在这项研究中，我们发现 TTK 在 77.63% (118/152) 的 HCC 标本中过度表达。 TTK 表达升高与肿瘤大小和门静脉癌栓 (PVTT) 的存在呈正相关。其启动子的去甲基化增加了 HCC 中 TTK 的表达。体外实验表明，TTK 不仅能促进细胞增殖和非贴壁依赖性生长，还能促进细胞迁移。随后的研究表明，TTK 以 p53 依赖性方式激活 Akt/mTOR 通路。我们还发现 TTK 特异性激酶抑制剂 AZ3146 可以减少 HCC 细胞的生长。总之，TTK 通过促进细胞增殖和迁移而促进 HCC 肿瘤发生。它可能作为一种新型生物标志物和 HCC 癌症治疗的潜在靶点。
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.