title: The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Baogang
authors.initials: B
authors.lastname: Peng
authors.forename: Lijian
authors.initials: L
authors.lastname: Liang
authors.forename: Jiaping
authors.initials: J
authors.lastname: Li
mesh_terms: D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D051881:Receptor, Notch1 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D051881:Receptor, Notch1