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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

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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 epithelial-mesenchymal transition; ERK1/2; hepatocellular carcinoma; β-catenin; snail
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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