A Switch in the Expression of Embryonic EMT-Inducers Drives the Development of Malignant Melanoma

作者：Caramel Julie; Papadogeorgakis Eftychios; Hill Louise; Browne Gareth J; Richard Geoffrey; Wierinckx Anne; Saldanha Gerald; O**orne Joy; Hutchinson Peter; Tse Gina; Lachuer Joel; Puisieux Alain; Pringle J Howard; Ansieau Stephane^*; Tulchinsky Eugene

来源：Cancer Cell, 2013, 24(4): 466-480.

DOI：10.1016/j.ccr.2013.08.018

Aberrant expression of embryonic epithelial-mesenchymal transition-inducing transcription factors (EMTTFs) in epithelial cells triggers EMT, neoplastic transformation, sternness, 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 nielanocyte 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.

• 出版日期2013-10-14