[Malignant melanoma and the role of the paradoxal protein Microphthalmia transcription factor]

Abstract

Mitf protein is a transcription factor involved all along the life of pigmented cells. This protein is located in the center of multiple signaling pathways which control differentiation, morphology, proliferation and survival of the various cells of the melanocyte lineage: melanoblasts, melanocytes and melanoma. Mitf plays a major role in melanoblasts differentiation, by inducing the key enzyme of melanogenesis, tyrosinase, and its secondary enzymes, Tyrp1 and Dct. Mitf regulates morphology and migration of melanocytes, particularly by regulating cytoskeleton organization and cell-cell adhesion. Mitf plays a double role of inducer/repressor of cellular proliferation. This protein inhibits cell cycle progression and prevents non-proper cell division. In few cases, Mitf can also induce cell cycle. A minimal quantity/activity of Mitf is necessary for melanoblast survival. Essential protein of the melanocyte lineage, Mitf was proposed as diagnostic/pronostic marker for cutaneous melanoma. However, could we then consider MITF as the unique marker of such a cancer?