title: BMP-7 blocks the effects of TGF-β-induced EMT in cholangiocarcinoma.
abstract: 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 β (TGF-β) 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-β 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-β-induced CCA cell migration, through inhibition of TGF-β-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.
authors: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors: Kassaporn
authors: K
authors: Duangkumpha
authors: Anchalee
authors: A
authors: Techasen
authors: Watcharin
authors: W
authors: Loilome
authors: Nisana
authors: N
authors: Namwat
authors: Raynoo
authors: R
authors: Thanan
authors: Narong
authors: N
authors: Khuntikeo
authors: Puangrat
authors: P
authors: Yongvanit
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D051879:Twist-Related Protein 1 / Q000378:metabolism
chemical_list: D055419:Bone Morphogenetic Protein 7; D015820:Cadherins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D016212:Transforming Growth Factor beta; D051879:Twist-Related Protein 1