Loss of E-cadherin promotes migration and invasion of cholangiocarcinoma cells and serves as a potential marker of metastasis

Tumour Biol. 2014 Sep;35(9):8645-52. doi: 10.1007/s13277-014-2087-6. Epub 2014 May 28.


Tumor progression is characterized by loss of cell adhesion and increase of invasion and metastasis. E-cadherin, a cell adhesion molecule, is frequently downregulated and has been proposed as an important mediator in epithelial-mesenchymal transition (EMT) in tumors. In this study, we investigated the expression of E-cadherin and its association with cancer invasion and prognosis in cholangiocarcinoma (CCA). Immunohistochemistry results demonstrated a statistically significant association between the positive metastasis status with low E-cadherin protein expression in human CCA tissues (P = 0.04). Statistical trends were identified for low E-cadherin level and shorter survival time (P = 0.08). Targeting the E-cadherin expression in CCA cells with siRNA caused upregulation of vimentin, a mesenchymal marker, and disappearance of the E-cadherin/β-catenin adhesion complex from cell membranes. Moreover, migration and invasion abilities of the cells were increased under this condition. These findings suggest that reduction of E-cadherin contributes to CCA progression by attenuating the strength of cellular adhesion, which affects motility as well as regulating the expression of EMT-related genes during CCA invasion and metastasis. Thus, E-cadherin can act as a central modulator of tumor cell phenotype and is a potential metastasis marker in CCA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Cell Movement*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism*
  • Cholangiocarcinoma / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis
  • RNA Interference
  • Tissue Array Analysis
  • Vimentin / metabolism
  • beta Catenin / metabolism


  • Biomarkers, Tumor
  • Cadherins
  • Vimentin
  • beta Catenin