Getting under the skin of melanomas

What makes melanomas one of the most dangerous forms of cancer is the speed and aggressiveness with which these skin cancers spread to other parts of the body. In about a third of melanomas, the protein ß-catenin is dysregulated, but the significance of this has been unclear. Now, Yale researchers have shown that ß-catenin helps drive melanomas’ aggressive metastasis.

In work described in the December issue of Cancer Cell, a team led by Marcus W. Bosenberg, M.D., Ph.D., associate professor of dermatology and pathology, studied mice with genetic mutations that make them extremely prone to melanomas. When these mice were further engineered to lack ß-catenin they didn’t develop melanomas as quickly, and their tumors did not spread to lymph nodes, as they usually do in this mouse model. When ß-catenin levels were increased by stabilizing the protein in melanoma cells, the mice developed severe skin tumors that spread to lymph nodes and lungs within a few weeks.

“This shows that a gene can enhance metastasis when activated and dramatically reduce metastasis when inactivated,” says Bosenberg, but “there is still much work to be done to see exactly how this happens.”