Overexpression of Rab5a promotes hepatocellular carcinoma cell proliferation and invasion via FAK signaling pathway

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• 作者：Donghua Geng ; Wenyan Zhao ; Yong Feng ; Jingang Liu
• 刊名：Tumor Biology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：37
• 期：3
• 页码：3341-3347
• 全文大小：613 KB
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380
• 卷排序：37

文摘

Rab5a was reported to be overexpressed in human malignancy and associated with the malignant phenotype. To data, its expression pattern and biological function in hepatocellular carcinoma (HCC) have not been studied. We analyzed Rab5a protein expression in 98 cases of HCC tissues and four HCC cell lines. We found that Rab5a expression was upregulated in HCC tissues and cell lines. Rab5a overexpression correlated with TNM stage and nodal metastasis (p < 0.05). To confirm the biological function of Rab5a in HCC cell lines, Rab5a siRNA was employed in SK-Hep-1 cell line and plasmid transfection was performed in Huh7 cell line. CCK-8 assay showed that Rab5a depletion blocked cell growth rate while Rab5a overexpression facilitated proliferation. Transwell and migration assay showed that Rab5a positively regulated cell invasion and migration. To explore the molecular mechanism underlying the biological effects of Rab5a, we checked several signaling pathways and found that Rab5a overexpression upregulated cyclin D1, cyclin E expression, FAK (Tyr397), and AKT (Ser473) phosphorylation. Blockage of FAK using inhibitor PF573228 abolished the role of Rab5a on cyclin D1. In conclusion, Rab5a is overexpressed in human HCC and contributes to cancer cell proliferation and invasion through regulation of FAK and AKT signaling.KeywordHepatocellular carcinomaRab5aFAK