The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma

BACKGROUND: Notch signaling, a critical pathway for tissue development, contributes to tumorigenesis in many tissues; however, the roles of Notch signaling in Intrahepatic Cholangiocarcinoma (ICC) remains unclear. In this study, we evaluated the expression and effects of Notch1 on cell migration in ICC. METHODS: Multiple cellular and molecular approaches were performed including gene transfection, siRNA transfection, RT-PCR, Western blotting, Rac activation assays and immunofluorescence. RESULTS: We found that Notch1 was up-regulated in ICC tissues and cell lines. The exogenous expression of Notch1 in glioma cells increased their migratory and invasive capacity. Similarly, the suppression of Notch1 expression inactivated Rac1 and inhibited ICC cell migration. Notch1 over expression induced an Epithelial-to-mesenchymal transition (EMT) phenotype that included enhanced expression of α-SMA and Vimentin, loss of E-cadherin expression, morphological changes and cytoskeletal reorganization in ICC cells. CONCLUSION: Notch1 may induce a migratory effect in ICC by causing an epithelial-mesenchymal transition and activating Rac1 and could serve as a novel diagnostic and therapeutic target in patients with ICC.