Figure 1.

Melanoma evolution and phenotype switching. Melanoma heterogeneity as the product of cell-intrinsic and microenvironmental driven ‘phenotype switching’. The role of epithelial-to-mesenchymal transition-inducing transcription factors (EMT-TFs) and of microphthalmia-associated transcription factor (MITF) is highlighted in the ‘phenotype switching’ model explaining melanoma evolution. The revised MITF rheostat model, including six different phenotypic states, explaining the oscillation between differentiated vs invasive melanoma cells through the reactivation of melanocyte differentiation program in melanoma is illustrated on the bottom.