MITF, the Janus transcription factor of melanoma.

Current models of melanoma propose that transition from the proliferative to the invasive stages of tumor development involves a dynamic and reversible switch in cell phenotype. The almost mutually exclusive proliferative and invasive phenotypes are defined by distinct gene expression signatures, which are themselves controlled by the level of functional MITF protein present in the cell. Recently, new signaling pathways and transcription factors that regulate MITF expression have been defined, and high throughput genomics have identified novel MITF target genes. MITF acts both as a transcription activator to promote expression of genes involved in cell cycle, but also as a transcriptional repressor of genes involved in invasion. A novel human germline mutation in MITF has been identified that blocks its sumoylation, thereby altering its transcriptional properties and conferring an increased risk of melanoma. These new studies depict an ever more complex function for MITF in melanoma.