A Switch in the Expression of Embryonic EMT-Inducers Drives the Development of Malignant Melanoma
A Switch in the Expression of Embryonic EMT-Inducers Drives the Development of Malignant Melanoma
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DOI：
10.1016/j.ccr.2013.08.018
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发表时间：
2013-10-14
期刊：
影响因子：
50.3
通讯作者：
Tulchinsky, Eugene
中科院分区：
文献类型：
--
作者：
Caramel, Julie;Papadogeorgakis, Eftychios;Tulchinsky, Eugene
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.
