Biomed Pharmacother 2018 Nov 01;107:1286-1293. doi: 10.1016/j.biopha.2018.08.011.

TPX2 level correlates with cholangiocarcinoma cell proliferation, apoptosis, and EMT.

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PURPOSE: The molecular signatures of cholangiocarcinoma are not well characterized. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) has been shown to promote oncogenesis in the context of several cancers; however, its' role in cholangiocarcinoma has not been studied. We evaluated the role of TPX2 in cholangiocarcinoma. METHODS: Expression levels of TPX2 in cholangiocarcinoma were assessed by immunohistochemistry. Potential correlations were assessed by Chi-squared test. Impact of TPX2 expression on cell proliferation, cell cycle, apoptosis, cell invasion and migration was investigated by CCK-8, flow cytometric analysis, and transwell assay, respectively. The expressions of cell-cycle, cell-apoptosis and EMT related target proteins were detected by immunoblotting. RESULTS: TPX2 expression in cholangiocarcinoma tissues was significantly higher than that paracancerous tissue (44.3% vs. 5.7%; P<0.01). Overexpression of TPX2 showed a positive correlation with TNM stage, lymph node metastasis, and prognosis of patients. Knockdown of TPX2 expression induced G2-M arrest, apoptosis and inhibited invasion and migration of cholangiocarcinoma cells. Treatment of cholangiocarcinoma cells with TPX2 siRNA resulted in upregulation of cyclin A1, cyclin B1, p53, Bax, and E-cadherin; while downregulation of cyclin D1, CDK2, Bcl-2, N-cadherin, β-cadherin MMP-2, MMP-9, Slug, and Twist1. CONCLUSIONS: Collectively, these results indicate that TPX2 may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for cholangiocarcinoma.

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Species referenced: Xenopus
Genes referenced: bax cck cdk2 itk snai2 tp53 tpx2 twist1

???displayArticle.disOnts??? cholangiocarcinoma