Researchers discover more than 40 melanoma-specific genes that determine aggressiveness

Researchers from the Spanish National Cancer Research Centre (CNIO) have discovered more than 40 genes that predict the level of aggressiveness of melanoma and distinguish it from other cancers with a poor prognosis. The discovery, published in Cancer Cell, will help to identify unique aspects of melanoma that could contribute to determining the risk of developing metastasis in patients with the disease.

The factors that are increased in melanoma share a mechanism: the formation of vesicles called endosomes. Endosomes are machinery that tumor cells, via a process called endocytosis, can use to incorporate components into their environment and obtain energy by degrading them via autodigestion or autophagy.

Among the genes that control endocytosis, study authors focused specifically on one, RAB7, which is highly expressed in melanoma cells. They showed that RAB7 determines the fate of melanoma cells; at high concentrations of RAB7, cellular autodigestion is very active, allowing tumor cells to obtain energy, prevent the accumulation of toxic components, and thus divide and proliferate. When RAB7 is reduced, cells use endosomes to recycle metastatic proteins, favoring their dispersal throughout the body.

The study results help researchers to understand the mechanism of action of a compound that, as the group discovered in 2009, is lethal in melanoma cells as well as in other tumor cells. This RNA-based nanoparticle compound kills the cells by acting on the formation of vesicles.

“We knew how our nanoparticles act inside tumor cells, but not how they selectively incorporate inside the cells,” says María Soengas, PhD, head of CNIO's Melanoma Group. The size of these molecules requires cells to form endosomes in order to be able to trap the compound. This study demonstrates that this endosome formation (via RAB7) is very active in tumor cells but not in normal cells. Read the study summary.