title: Loss of vinculin and membrane-bound β-catenin promotes metastasis and predicts poor prognosis in colorectal cancer.
abstract: BACKGROUND
  Loss 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Vinculin 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.
  
  
  CONCLUSIONS
  Our 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Hanqing
authors.initials: H
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Zhao
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Sijun
authors.initials: S
authors.lastname: Hu
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology & State Key Laboratory of Cancer Biology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. kaicwu@fmmu.edu.cn.
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D011379:Prognosis; D016596:Vinculin / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin; D016596:Vinculin