Kindlin-2 promotes hepatocellular carcinoma invasion and metastasis by increasing Wnt/β-catenin signaling

Background: kindlin-2 is a member of the focal adhesion protein family that regulates invasion and metastasis in multiple malignancies; however,little is known about the role of kindlin-2 in hepatocellular carcinoma (hcc) progression. methods: immunohistochemistry was used to investigate kindlin-2 expression in 177 pairs of human hcc and adjacent liver tissue samples. the role of kindlin-2 in the in vitro invasion and migration of hcc cell lines was evaluated in mhcc97h,lm3 and smmc7721 cells. microarray expression analysis was applied to explore the molecular mechanism through which kindlin-2 promoted hcc progression. quantitative real-time pcr and western blotting were performed to verify the microarray results. results: high kindlin-2 expression was found to significantly correlate with aggressive hcc clinicopathological features including tumor encapsulation,microvascular invasion,extrahepatic metastasis and poor prognosis. in vitro,kindlin-2 knockout or knockdown inhibited hcc cell adhesion,migration and invasion,while ectopic kindlin-2 expression promoted these processes. importantly,kindlin-2 activated wnt/β-catenin signaling and increased β-catenin expression,especially levels of non-phosphorylated β-catenin,as well as two wnt/β-catenin signaling pathway targets,axin2 and mmp7. kindlin-2 also induced a change in the expression profile of hcc cells,suggesting the cells underwent epithelial-mesenchymal transition. for example,the expression of the epithelial marker e-cadherin was downregulated,while the mesenchymal markers vimentin,n-cadherin and snail were upregulated. conclusion: kindlin-2 promotes hcc invasion,metastasis and epithelial-mesenchymal transition through wnt/β-catenin signaling. © 2017 the author(s).