The three M's: melanoma, microphthalmia-associated transcription factor and microRNA.

Studies examining intratumor heterogeneity have indicated that several cancer types, including melanoma, can display phenotypic plasticity, corresponding to their capacity to undergo transient reversible cellular changes. Conceptual models constructed to explain the process of cancer propagation differ in their treatment of intratumor heterogeneity. Recent observations of reversible phenotypic heterogeneity in melanoma have led to the proposal of a novel 'phenotypic plasticity' model of cancer propagation. Microphthalmia-associated transcription factor (MITF), the melanocyte 'lineage-specific' transcription factor, has emerged as one of the central players in melanoma phenotypic plasticity. Here we discuss the conceptual models suggested to explain the relations between MITF and melanoma plasticity, in addition to the complex regulatory roles that MITF plays in melanocytes and melanoma development. Finally, we provide an in-depth literature survey of microRNAs (miRNAs) involved in MITF activity, melanoma propagation and metastasis, in addition to their potential use as agents of personalized therapy. 2011 John Wiley & Sons A/S.