Fascin Induces Epithelial-Mesenchymal Transition of Cholangiocarcinoma Cells by Regulating Wnt/β-Catenin Signaling
Xianhai Mao, Xiaohui Duan, Bo Jiang
(Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, Changsha, Hunan, China (mainland))
Med Sci Monit 2016; 22:3479-3485
Our preliminary study suggested that the expression of Fascin was increased in cholangiocarcinoma, which indicating poor prognosis The present study aimed to explore the roles and mechanisms of Fascin during the progression of cholangiocarcinoma.
MATERIAL AND METHODS: We evaluated the knockdown effect of endogenous Fascin expression by Short hairpin RNA (shRNA) in QBC939 cells. Cell proliferation was confirmed by MTS assay. Migration and invasion assay was used to examine the cell invasive ability. Tumorigenesis abilities in vivo were analyzed with a xenograft tumor model. Western blot analysis was used to test epithelial-mesenchymal transition (EMT) biomarkers and critical proteins in the Wnt/β-catenin signaling pathway.
RESULTS: shRNA-mediated gene knockdown of Fascin significantly inhibited cell proliferation, invasion, and EMT, and shRNA-Fascin markedly inhibited the xenograft tumor volume. Silencing of Fascin up-regulated phosphorylation of β-catenin and decreased its nuclear localization. Additionally, knockdown of Fascin led to the upregulation of β-catenin and E-cadherin expression in plasma membrane fraction of QBC939 cells.
CONCLUSIONS: Our data indicate a key role of Fascin in cell proliferation, migration, and invasion in cholangiocarcinoma. Fascin promotes EMT of cholangiocarcinoma cells, in part through regulating Wnt/β-catenin signaling.
Keywords: Cholangiocarcinoma, Epithelial-mesenchymal transition, RNA, Small Interfering