| Literature DB >> 24075834 |
Julie Caramel1, Eftychios Papadogeorgakis, Louise Hill, Gareth J Browne, Geoffrey Richard, Anne Wierinckx, Gerald Saldanha, Joy Osborne, Peter Hutchinson, Gina Tse, Joël Lachuer, Alain Puisieux, J Howard Pringle, Stéphane Ansieau, Eugene Tulchinsky.
Abstract
Aberrant expression of embryonic epithelial-mesenchymal transition-inducing transcription factors (EMT-TFs) in epithelial cells triggers EMT, neoplastic transformation, stemness, and metastatic dissemination. We found that regulation and functions of EMT-TFs are different in malignant melanoma. SNAIL2 and ZEB2 transcription factors are expressed in normal melanocytes and behave as tumor-suppressor proteins by activating an MITF-dependent melanocyte differentiation program. In response to NRAS/BRAF activation, EMT-TF network undergoes a profound reorganization in favor of TWIST1 and ZEB1. This reversible switch cooperates with BRAF in promoting dedifferentiation and neoplastic transformation of melanocytes. We detected EMT-TF reprogramming in late-stage melanoma in association with enhanced phospho-ERK levels. This switch results in E-cadherin loss, enhanced invasion, and constitutes an independent factor of poor prognosis in melanoma patients.Entities:
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Year: 2013 PMID： 24075834 DOI： 10.1016/j.ccr.2013.08.018
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743