期刊
TUMOR BIOLOGY
卷 35, 期 10, 页码 9667-9676出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-014-2246-9
关键词
Twist; N-cadherin; Metastasis; Epithelial-mesenchymal transition; BMP-7; Cholangiocarcinoma
类别
资金
- Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Health Cluster (SHeP-GMS), Khon Kaen University, Khon Kaen University Research Fund [M54206]
- Faculty of Medicine [I 56316]
Epithelial-mesenchymal transition (EMT) is characterized by the loss of epithelial markers and the gain of mesenchymal markers. EMT is believed to be a major mechanism supporting cancer cell metastasis. The activation of EMT can be induced by various types of inflammatory cytokines including transforming growth factor beta (TGF-beta) whereas bone morphogenetic protein-7 (BMP-7) can inhibit this process. In this study, the up-regulation of Twist transcription factor and N-cadherin, mesenchymal marker in CCA tissues, has been demonstrated and it has been found that the high expression of Twist was significantly associated with poor prognosis of CCA patients (P=0.010). Moreover, CCA samples showing Twist nuclear expression were significantly correlated with the up-regulation of N-cadherin (P=0.024). These results also showed that the inflammatory mediator TGF-beta induces CCA cell migration, one of the metastatic processes possibly via stimulation of Twist, N-cadherin and vimentin expression. Additionally, it has been shown that BMP-7 inhibits TGF-beta-induced CCA cell migration, through inhibition of TGF-beta-mediated Twist and N-cadherin expressions. These data reinforce the rationale to use BMP-7 as an EMT inhibitor to suppress the progression of CCA and might be a therapeutic approach to improve efficiency for CCA treatment.
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