Scientists Discover Gene That May Cause Melanoma to Metastasize

A new study published Monday by scientists at the University of Massachusetts Medical School (UMMS) in Boston reports findings on a gene that is responsible for creating a protein that may help melanoma to grow and metastasize. The study appears in the Journal of Clinical Investigation.

Researchers found 374 genes that were altered in zebrafish melanomas as well as human melanomas. GDF6 is a part of a class of proteins that are active during embryo development, called “growth differentiation factors.” In looking at human melanoma cells, researchers found that 80% of patient tumors had elevated levels of GDF6, and the level of the protein in a tumor correlated to the aggressiveness of the cancer. By comparison, for people with lower levels of GDF6, melanoma was less likely to metastasize, according to the study.

“Melanoma is an aggressive cancer and the most deadly form of skin cancer,” Craig J. Ceol, PhD, an assistant professor of molecular medicine at UMMS, said in a statement. “Although new therapies have shown effectiveness against melanoma, a majority of patients either do not respond to these therapies or develop resistance. What is so exciting about this discovery, is that it opens up a completely new therapeutic target for investigation. None of the current therapies on the market target GDF6 or its pathway. For patients with very aggressive or treatment-resistant forms of cancer, this is very important; there is great therapeutic potential when you combine a drug targeting GDF6 with current therapeutics.”

Though melanoma is very aggressive, it accounts for only around 1% of all skin cancers. The National Cancer Institute (NCI) estimates that 87,110 new cases of melanoma were diagnosed in 2017.

Ceol and his colleagues are currently looking at a way to “switch off” the gene that could potentially be used in a clinical setting. “Because GDF6 is a type of protein that acts outside the cell, it makes it much easier to target therapeutically. We’re already exploring how to use monoclonal antibodies to inhibit GDF6,” Ceol said.

Reference

Venkatesan AM, Vyas R, Grammann AK, et al. Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma [published online, December 4, 2017]. J Clin Invest. 2017; doi:10.1172/JCI92513