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).

CONCLUSION:

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: K Araki, T Shimura, H Suzuki, S Tsutsumi, W Wada, T Yajima, T Kobayahi, N Kubo, H Kuwano
• Journal: British journal of cancer (Br J Cancer) Vol. 105 Issue 12 Pg. 1885-93 (Dec 06 2011) ISSN: 1532-1827 [Electronic] England
• PMID: 22068819 (Publication Type: Journal Article)

Chemical References

• Cadherins
• Transforming Growth Factor beta

Topics

• Aged
• Blotting, Western
• Cadherins (metabolism)
• Cell Proliferation
• Cholangiocarcinoma (metabolism, pathology)
• Disease Progression
• Electrophoresis, Polyacrylamide Gel
• Epithelial-Mesenchymal Transition
• Female
• Fluorescent Antibody Technique
• Humans
• Immunohistochemistry
• Male
• Microscopy, Confocal
• Middle Aged
• Signal Transduction
• Transforming Growth Factor beta (physiology)