Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-263) contains supplementary material, which is available to authorized users.
Highlights
Loss of cell-cell adhesion is important for the development of cancer invasion and metastasis
Our results suggest that vinculin may play specific roles in the epithelial-mesenchymal transition (EMT) and metastasis of colorectal cancer (CRC) and that loss of vinculin could be used as a prognostic factor for CRC
Vinculin expression is downregulated in CRC cell lines and inversely correlated with CRC metastasis To examine the significance of vinculin in CRC carcinogenesis, we measured the expression of vinculin in five human CRC cell lines (HCT116, Caco2, HT29, SW620 and SW480) and in HIEC, an immortalised colon epithelial cell line
Summary
Loss of cell-cell adhesion is important for the development of cancer invasion and metastasis. Loss of vinculin has been found in the development of many cancers, such as squamous carcinoma [11,12], rhabdomyosarcoma [13] and breast cancer [14], implying that vinculin may have anti-tumour effects. Recent studies confirmed this finding, as vinculin inhibited multiple processes associated with malignant tumours, including invasion, metastasis and apoptosis [8,15]. Low levels of vinculin may predict poor survival in squamous cell cancer [12], but the biological role of vinculin and its prognostic value in CRC have not been fully investigated
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