title: Crosstalk between beta-catenin and snail in the induction of epithelial to mesenchymal transition in hepatocarcinoma: role of the ERK1/2 pathway.
abstract: Epithelial to mesenchymal transition (EMT) is an integral process in the progression of many epithelial tumors. It involves a coordinated series of events, leading to the loss of epithelial features and the acquisition of a mesenchymal phenotype, resulting in invasion and metastasis. The EMT of hepatocellular carcinoma (HCC) cells is thought to be a key event in intrahepatic dissemination and distal metastasis. In this study, we used 12-O-tet-radecanoylphorbol-13-acetate (TPA) to dissect the signaling pathways involved in the EMT of HepG2 hepatocarcinoma cells. The spectacular change in phenotype induced by TPA, leading to a pronounced spindle-shaped fibroblast-like cell morphology, required ERK1/2 activation. This ERK1/2-dependent EMT process was characterized by a loss of E-cadherin function, modification of the cytoskeleton, the acquisition of mesenchymal markers and profound changes to extracellular matrix composition and mobility. Snail was essential for E-cadherin repression, but was not sufficient for full commitment of the TPA-triggered EMT. We found that TPA triggered the formation of a complex between Snail and β-catenin that activated the Wnt pathway. This study thus provides the first evidence for the existence of a complex network governed by the ERK1/2 signaling pathway, converging on the coregulation of Snail and the Wnt/β-catenin pathway and responsible for the onset and the progression of EMT in hepatocellular carcinoma cells.
authors.affiliation: Laboratory of Xenobiotic's Cellular and Molecular Toxicology, INRA, UMR 1331 TOXALIM (Research Centre in Food Toxicology), Sophia Antipolis 06903, France. ludovic.peyre@sophia.inra.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Zucchini-Pascal
authors.forename: Ludovic
authors.initials: L
authors.lastname: Peyre
authors.forename: Roger
authors.initials: R
authors.lastname: Rahmani
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D056945:Hep G2 Cells; D018197:Hepatoblastoma / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin