Transcription factors, extensively described for their role in epithelial-mesenchymal transition (EMT-TFs) in epithelial cells, also display essential functions in the melanocyte lineage. Recent evidence has shown specific expression patterns and functions of these EMT-TFs in neural crest-derived melanoma compared to carcinoma. Herein, we present an update of the specific roles of EMT-TFs in melanocyte differentiation and melanoma progression. As major regulators of phenotype switching between differentiated/proliferative and neural crest stem cell-like/invasive states, these factors appear as major drivers of intra-tumor heterogeneity and resistance to treatment in melanoma, which opens new avenues in terms of therapeutic targeting.
Keywords: EMT; ZEB2/ZEB1 switch; intra-tumor heterogeneity; melanocyte differentiation; melanoma development; neural-crest stem cells; phenotype switching; resistance to treatment; transcription factors.