title: Loss of ezrin in human intrahepatic cholangiocarcinoma is associated with ectopic expression of E-cadherin.
abstract: OBJECTIVE
  Ezrin connects proteins from the plasma membrane to the subcortical cytoskeleton, and contributes to epithelial integrity by interacting with the cell-cell adhesion molecule E-cadherin. In the liver, ezrin is restricted to cholangiocytes, where it regulates biliary secretory functions. During carcinogenesis, ezrin expression is impaired and associated with enhancement of cell migratory activity in cancer cells; therefore, we aimed to analyse ezrin in cholangiocarcinogenesis.
  
  
  RESULTS
  Ezrin expression was evaluated by immunohistochemistry on tissue microarrays from 94 surgical specimens of intrahepatic cholangiocarcinoma (CCA), and correlated with clinicopathological factors and E-cadherin expression. Ezrin function was also analysed in human CCA cell lines. In CCA, ezrin was negative/weakly expressed in 49 cases (52%) and moderately/strongly expressed in 45 cases (48%), mostly in cell cytoplasm. The negative/weak expression of ezrin was more frequent in peripheral than in perihilar CCA (P = 0.002), and was associated with high tumour size (P = 0.001), low mucus secretion (P = 0.042), the presence of satellite nodules (P = 0.024), and ectopic cytoplasmic expression of E-cadherin (P = 0.005). In vitro, silencing of ezrin in CCA cells caused internalization of E-cadherin and favoured cell migration.
  
  
  CONCLUSIONS
  Ezrin is down-regulated during cholangiocarcinogenesis, and its loss results in a more aggressive phenotype.
authors.affiliation: Service d'anatomie pathologique Hôpital Beaujon, Clichy, France.|INSERM, UMR 1149, Centre de Recherche sur l'Inflammation, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guedj
authors.affiliation: INSERM, UMR_S 938, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.
authors.forename: Javier
authors.initials: J
authors.lastname: Vaquero
authors.affiliation: INSERM, UMR_S 938, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Clapéron
authors.affiliation: INSERM, UMR_S 938, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Mergey
authors.affiliation: INSERM, UMR_S 938, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Chrétien
authors.affiliation: Service d'anatomie pathologique Hôpital Beaujon, Clichy, France.|INSERM, UMR 1149, Centre de Recherche sur l'Inflammation, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
authors.affiliation: INSERM, UMR_S 938, Paris, France.|Sorbonne Universités, UPMC Université Paris 06, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Fouassier
mesh_terms: D000368:Aged; D015703:Antigens, CD; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D000066630:Ectopic Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D046888:Tissue Array Analysis; D000099149:Ezrin
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins; D003598:Cytoskeletal Proteins; D000099149:Ezrin; C513384:CDH1 protein, human
keywords: E-cadherin; cellular biology; cholangiocarcinoma; ezrin; immunohistochemistry