title: Loss of E-cadherin promotes migration and invasion of cholangiocarcinoma cells and serves as a potential marker of metastasis.
abstract: Tumor progression is characterized by loss of cell adhesion and increase of invasion and metastasis. E-cadherin, a cell adhesion molecule, is frequently downregulated and has been proposed as an important mediator in epithelial-mesenchymal transition (EMT) in tumors. In this study, we investigated the expression of E-cadherin and its association with cancer invasion and prognosis in cholangiocarcinoma (CCA). Immunohistochemistry results demonstrated a statistically significant association between the positive metastasis status with low E-cadherin protein expression in human CCA tissues (P = 0.04). Statistical trends were identified for low E-cadherin level and shorter survival time (P = 0.08). Targeting the E-cadherin expression in CCA cells with siRNA caused upregulation of vimentin, a mesenchymal marker, and disappearance of the E-cadherin/β-catenin adhesion complex from cell membranes. Moreover, migration and invasion abilities of the cells were increased under this condition. These findings suggest that reduction of E-cadherin contributes to CCA progression by attenuating the strength of cellular adhesion, which affects motility as well as regulating the expression of EMT-related genes during CCA invasion and metastasis. Thus, E-cadherin can act as a central modulator of tumor cell phenotype and is a potential metastasis marker in CCA.
authors.affiliation: Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Anchalee
authors.initials: A
authors.lastname: Techasen
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
authors.forename: Nisana
authors.initials: N
authors.lastname: Namwat
authors.forename: Narong
authors.initials: N
authors.lastname: Khuntikeo
authors.forename: Anucha
authors.initials: A
authors.lastname: Puapairoj
authors.forename: Patcharee
authors.initials: P
authors.lastname: Jearanaikoon
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
mesh_terms: D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D034622:RNA Interference; D046888:Tissue Array Analysis; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D014746:Vimentin; D051176:beta Catenin