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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2017

Open Access 01-12-2017 | Research

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

Authors: Jie Lin, Wansong Lin, Yunbin Ye, Liping Wang, Xiaoyan Chen, Shengbing Zang, Aimin Huang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2017

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Abstract

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.
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Metadata
Title
Kindlin-2 promotes hepatocellular carcinoma invasion and metastasis by increasing Wnt/β-catenin signaling
Authors
Jie Lin
Wansong Lin
Yunbin Ye
Liping Wang
Xiaoyan Chen
Shengbing Zang
Aimin Huang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2017
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-017-0603-4

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