Next Article in Journal
Lipid Transport and Metabolism in Healthy and Osteoarthritic Cartilage
Next Article in Special Issue
Cancer Development, Progression, and Therapy: An Epigenetic Overview
Previous Article in Journal
Molecular Cloning, Sequence Characterization and Expression Analysis of a CD63 Homologue from the Coleopteran Beetle, Tenebrio molitor
Previous Article in Special Issue
Glycogen Synthase Kinase 3β Inhibition as a Therapeutic Approach in the Treatment of Endometrial Cancer
Article Menu

Export Article

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

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 / Revised: 23 September 2013 / Accepted: 3 October 2013 / Published: 16 October 2013
(This article belongs to the Special Issue Molecular Research of Carcinogenesis)
View Full-Text   |   Download PDF [1241 KB, uploaded 19 June 2014]   |  


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. View Full-Text
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 (CC BY 3.0).

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top