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నైరూప్య

The Many Roles of MITF in Melanoma

Jiri Vachtenheim

Microphthalmia-associated transcription factor (MITF) plays pivotal role in the maintenance of the melanocyte lineage, differentiation of normal and malignant melanocytes and the survival of melanoma cells. MITF regulates expression of many genes with critical functions in cell differentiation, proliferation, and pro-survival properties. Melanoma is an extremely resilient tumor for which no effective therapy exists when the tumor progresses into metastasis. Melanoma is a heterogenous tumor in which the microheterogeneity arises already in the first stages of the tumor development. Because the dependence of the melanocyte lineage on MITF is critical, MITF is regarded as the paradigmatic lineage-addiction oncogene and its gene is amplified in a smaller subset of melanomas. The level of MITF protein greatly differs among the tumor cells. Intriguingly, low MITF level cells are slowly proliferating but constitute an invasive subpopulation of tumor cells. In this minireview, I briefly discuss the many roles and activities of MITF in melanoma cells and the future prospects for melanoma therapy.