Melanocyte differentiation is under the control of microphthalmia-associated transcription factor (MITF), a lineage survival oncogene mediating pro-proliferative function in malignant melanoma. Paradoxically, however, high expression of MITF also has an anti-proliferative effect. Scientists at Keio University School of Medicine, Shinjuku-ku, Tokyo and collaborators have demonstrated that both depletion and forced expression of MITF in human melanoma cell lines significantly inhibited proliferation. Although approximately half of the cell lines were resistant to MITF depletion, simultaneous depletion of both MITF and BRAFV600E, an oncogenic kinase also associated with melanoma, significantly inhibited melanoma growth even in the resistant cell lines. The work, published in the October edition of Cancer Science, suggests that dual inhibition of MITF and BRAFV600E represents a useful strategy for treatment of melanoma.
A second study, from collaborators at The Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation, has found that the receptor tyrosine kinase, TYRO3, is an upstream regulator of MITF expression. TYRO3 expression is significantly elevated in human primary melanoma tissue samples and melanoma cell lines and correlates with MITF mRNA levels. Their study showed that TYRO3 overexpression bypassed BRAFV600E-induced senescence in primary melanocytes, inducing transformation of non-tumourigenic cell lines. Knockdown of TYRO3 repressed cellular proliferation of melanoma cells and sensitised them to chemotherapy-induced apoptosis. In addition, TYRO3 knockdown in melanoma cells also inhibited tumourigenesis in vivo. The study is published in the 23rd September online edition of PNAS.
Taken together, the two studies suggest that a dual TYRO3/ BRAFV600E inhibitor would be interesting to evaluate in melanoma.
Malignant Melanoma is a type of cancer which originates on skin. It can appear as a mole. It is even found in younger age bracket. It appears in the leg for females and for males, it is found on chest or back area. Those who have dark skin tone, are less likely to develop melanoma. Immediately diagnosing is very important, else it can worsen the situation. If anyone observes symptoms of it, should consult to doctor immediately.