title: E/N-cadherin switch mediates cancer progression via TGF-β-induced epithelial-to-mesenchymal transition in extrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  Epithelial-to-mesenchymal transition (EMT) is a fundamental process governing not only morphogenesis in multicellular organisms, but also cancer progression. During EMT, epithelial cadherin (E-cadherin) is downregulated while neural cadherin (N-cadherin) is upregulated, referred to as 'cadherin switch'. This study aimed to investigate whether cadherin switch promotes cancer progression in cholangiocarcinoma (CC).
  
  
  METHODS
  CC cell lines were examined for migration, invasion, and morphological changes with typical EMT-induced model using recombinant TGF-β1. The changes in E-cadherin and N-cadherin expression were investigated during EMT. We also examined E-cadherin and N-cadherin expression in resected specimens from extrahepatic CC patients (n=38), and the associations with clinicopathological factors and survival rates.
  
  
  RESULTS
  TGF-β1 treatment activated cell migration, invasion, and fibroblastic morphological changes, especially in extrahepatic CC HuCCT-1 cells. These changes occurred with E-cadherin downregulation and N-cadherin upregulation, that is, cadherin switch. Patients with low E-cadherin expression had a significantly lower survival rate than patients with high E-cadherin expression (P=0.0059). Patients with decreasing E-cadherin and increasing N-cadherin expression had a significantly lower survival rate than patients with increasing E-cadherin and decreasing N-cadherin expression (P=0.017).
  
  
  CONCLUSIONS
  Cadherin switch promotes cancer progression via TGF-β-induced EMT in extrahepatic CC, suggesting a target for elucidating the mechanisms of invasion and metastasis in extrahepatic CC.
authors: Department of General Surgical Science (Surgery 1), Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, Japan. karaki@showa.gunma-u.ac.jp
authors: K
authors: K
authors: Araki
authors: T
authors: T
authors: Shimura
authors: H
authors: H
authors: Suzuki
authors: S
authors: S
authors: Tsutsumi
authors: W
authors: W
authors: Wada
authors: T
authors: T
authors: Yajima
authors: T
authors: T
authors: Kobayahi
authors: N
authors: N
authors: Kubo
authors: H
authors: H
authors: Kuwano
mesh_terms: D000368:Aged; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D015820:Cadherins; D016212:Transforming Growth Factor beta