Loss of vinculin and membrane-bound β-catenin promotes metastasis and predicts poor prognosis in colorectal cancer

Molecular Cancer

Research

Daiming Fan¹  Sijun Hu¹  Kaichun Wu¹  Yongquan Shi¹  Ting Li¹  Xiaodi Zhao¹  Yuanyuan Lu¹  Yongzhan Nie¹  Hanqing Guo²  Ying Song² 

[1] Department of Gastroenterology & State Key Laboratory of Cancer Biology, Xijing Hospital, The Fourth Military Medical University, 710032, Xi’an, China;Department of Gastroenterology, Xi’an Central Hospital, College of Medicine, Xi’an Jiaotong University, Xi’an, Shanxi, China;

关键词: Vinculin;    β-catenin;    Colorectal cancer;    Metastasis;    Prognosis;    EMT;   

DOI  :  10.1186/1476-4598-13-263

 received in 2014-07-23, accepted in 2014-11-27,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundLoss of cell-cell adhesion is important for the development of cancer invasion and metastasis. Vinculin, a key adhesion-related protein, can affect metastasis and prognosis in several tumours. Here, we determined the biological roles of vinculin in the metastasis of colorectal cancer (CRC) and evaluated its clinical significance as a potential disease biomarker.MethodsThe expression level of vinculin in CRC cell lines and tissues was measured using Real-Time PCR and western blotting. Moreover, vinculin function was analysed using Transwell assays and in vivo metastasis assays in gain- and loss-of-function experiments. Furthermore, the impact of vinculin together with membrane-bound β-catenin on the prognosis of 228 CRC patients was investigated by immunohistochemistry. Additionally, the expression of epithelial-mesenchymal transition (EMT) indicators was verified by immunohistochemistry in CRC tissues obtained from these patients.ResultVinculin expression was found to be significantly downregulated in highly metastatic CRC cell lines and metastatic tissues. Both in vitro and in vivo experiments showed that vinculin suppressed invasion, migration and metastasis in CRC cells and that this suppression could be attenuated by silencing β-catenin. Moreover, the expression of vinculin and membrane-bound β-catenin were positively correlated in CRC tissues, and lack of vinculin expression emerged as an independent prognostic factor in patients with CRC. Finally, the loss of vinculin and membrane-bound β-catenin was associated with node metastasis, organ metastasis and expression of EMT indicators.ConclusionOur results suggest that vinculin may play specific roles in the EMT and metastasis of CRC and that loss of vinculin could be used as a prognostic factor for CRC.

【 授权许可】

Unknown   
© Li et al.; licensee BioMed Central. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.