Microphthalmia-associated transcription factor in melanoma development and MAP-kinase pathway targeted therapy

Malignant melanoma is a neoplasm of melanocytes, and the microphthalmia-associated transcription factor (MITF) is essential for the existence of melanocytes. MITF's relevance for this cell lineage is maintained in melanoma, where it is an important regulator of survival and balances melanoma cell proliferation with terminal differentiation (pigmentation). The MITF gene is amplified in ~20% of melanomas and MITF mutation can predispose to melanoma development. Furthermore, the regulation of MITF expression and function is strongly linked to the BRAF/MEK/ERK/MAP-kinase (MAPK) pathway, which is deregulated in >90% of melanomas and central target of current therapies. MITF expression in melanoma is heterogeneous, and recent findings highlight the relevance of this heterogeneity for the response of melanoma to MAPK pathway targeting drugs, as well as for MITF's role in melanoma progression. This review aims to provide an updated overview on the regulation of MITF function and plasticity in melanoma with a focus on its link to MAPK signaling.