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Title: A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma
Authors: Caramel, Julie
Papadogeorgakis, Eftychios
Hill, Louise
Browne, Gareth J.
Richard, Geoffrey
Wierinckx, Anne
Saldanha, Gerald Saldanha
Osborne, Joy
Hutchinson, Peter
Tse, Gina
Lachuer, Joël
Puisieux, Alain
Pringle, J. Howard
Ansieau, Stéphane
Tulchinsky, Eugene
First Published: 26-Sep-2013
Publisher: Elsevier (Cell Press)
Citation: Cancer Cell, 2013, 24 (4), pp. 466-480
Abstract: Aberrant expression of embryonic epithelial-mesenchymal transition-inducing transcription factors (EMTTFs) 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.
DOI Link: 10.1016/j.ccr.2013.08.018
ISSN: 1535-6108
eISSN: 1878-3686
Type: Journal Article
Description: Full text of this item is not currently available on the LRA. The final published version may be available through the links above.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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