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. 2013 Oct 14;24(4):466-80.
doi: 10.1016/j.ccr.2013.08.018. Epub 2013 Sep 26.

A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma

Julie Caramel  1 , 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
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Free article

A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma

Julie Caramel et al. Cancer Cell. .
Free article

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.

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Comment in

  • 'TWIST and switch' metastasis.
    Roesch A. Roesch A. Pigment Cell Melanoma Res. 2014 Mar;27(2):157-8. doi: 10.1111/pcmr.12198. Epub 2013 Dec 16. Pigment Cell Melanoma Res. 2014. PMID: 24283630 No abstract available.
  • Plasticity of melanoma and EMT-TF reprogramming.
    Tulchinsky E, Pringle JH, Caramel J, Ansieau S. Tulchinsky E, et al. Oncotarget. 2014 Jan 15;5(1):1-2. doi: 10.18632/oncotarget.1662. Oncotarget. 2014. PMID: 24369126 Free PMC article. No abstract available.

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