Int. J. Mol. Sci. 2013, 14(10), 20768-20792; doi:10.3390/ijms141020768
Article

Crosstalk between Beta-Catenin and Snail in the Induction of Epithelial to Mesenchymal Transition in Hepatocarcinoma: Role of the ERK1/2 Pathway

Laboratory of Xenobiotic's Cellular and Molecular Toxicology, INRA, UMR 1331 TOXALIM (Research Centre in Food Toxicology), Sophia Antipolis 06903, France These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 9 July 2013; in revised form: 23 September 2013 / Accepted: 3 October 2013 / Published: 16 October 2013
(This article belongs to the Special Issue Molecular Research of Carcinogenesis)
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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.
Keywords: epithelial-mesenchymal transition; ERK1/2; hepatocellular carcinoma; β-catenin; snail

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MDPI and ACS Style

Zucchini-Pascal, N.; Peyre, L.; Rahmani, R. Crosstalk between Beta-Catenin and Snail in the Induction of Epithelial to Mesenchymal Transition in Hepatocarcinoma: Role of the ERK1/2 Pathway. Int. J. Mol. Sci. 2013, 14, 20768-20792.

AMA Style

Zucchini-Pascal N, Peyre L, Rahmani R. Crosstalk between Beta-Catenin and Snail in the Induction of Epithelial to Mesenchymal Transition in Hepatocarcinoma: Role of the ERK1/2 Pathway. International Journal of Molecular Sciences. 2013; 14(10):20768-20792.

Chicago/Turabian Style

Zucchini-Pascal, Nathalie; Peyre, Ludovic; Rahmani, Roger. 2013. "Crosstalk between Beta-Catenin and Snail in the Induction of Epithelial to Mesenchymal Transition in Hepatocarcinoma: Role of the ERK1/2 Pathway." Int. J. Mol. Sci. 14, no. 10: 20768-20792.

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