論文 - 詳細
| RRC ID | 68651 |
|---|---|
| 著者 | Araki K, Shimura T, Suzuki H, Tsutsumi S, Wada W, Yajima T, Kobayahi T, Kubo N, Kuwano H. |
| タイトル | E/N-cadherin switch mediates cancer progression via TGF-β-induced epithelial-to-mesenchymal transition in extrahepatic cholangiocarcinoma. |
| ジャーナル | Br J Cancer |
| 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. |
| 巻・号 | 105(12) |
| ページ | 1885-93 |
| 公開日 | 2011-12-6 |
| DOI | 10.1038/bjc.2011.452 |
| PII | bjc2011452 |
| PMID | 22068819 |
| PMC | PMC3251878 |
| MeSH | Aged Blotting, Western Cadherins / metabolism* Cell Proliferation Cholangiocarcinoma / metabolism Cholangiocarcinoma / 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* |
| IF | 5.791 |
| リソース情報 | |
| ヒト・動物細胞 | HuCCT1(RCB1960) TFK-1(RCB2537) HuH-28(RCB1943) |