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

Caramel J et al.

Cancer Cell Volume 24, Issue 4, 14 October 2013, Pages 466–480

Editor's comments:
Shading light on the EMT equivalent in melanoma Epithelial-mesenchymal transition is a phenomenon described for epithelial cancers, which allows tumor cells to achieve motility and invasiveness, typically associated with reduced proliferation and reduced differentiation. This process is a link between tumor cell proliferation and stemness and explains the transcriptional plasticity of tumor cells. Caramel et al. have now illustrated the impact of the MAP kinase pathway in this context. The data show that the activated MAP kinase pathways governs EMT transcription factors in melanoma.


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.