Uncovering the Role of BMP Signaling in Melanocyte Development and Melanoma Tumorigenesis
Technical Report,01 Jul 2013,30 Jun 2016
University of Massachusetts Medical School Worcester United States
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Melanoma is the most aggressive and lethal form of skin cancer. In 2013 over 75,000 Americans were diagnosed with melanoma, and nearly 10,000 died from this disease. It has been known for over a decade that mutations that over activate the BRAF and NRAS genes promote melanoma formation. At the same time it has also become clear that these mutations are not sufficient for melanoma formation and other genes are involved. Using genomic studies and cross-species comparisons, we identified the BMP factor GDF6 as a gene that may cooperate with mutant BRAF to promote melanoma. The aims of this grant are to determine if GDF6 does in fact cooperate with mutant BRAF and uncover the mechanisms by which GDF6 acts in melanomas and normal melanocytes. Toward these aims, we have used our zebra fish model to demonstrate cooperativity between GDF6 and mutant BRAF in accelerating melanoma onset. Furthermore, we have knocked down GDF6 in human melanoma cells, finding that loss of GDF6 causes cells to cease proliferating. These and other data suggest that GDF6 promotes melanoma progression and its withdrawal is detrimental to melanoma cell growth. We are currently investigating whether blocking GDF6 function is a viable therapeutic strategy.
- Medicine and Medical Research