Investigators from Weill Cornell Medicine have discovered a defense mechanism that protects skin cancer cells from oxidative stress and helps them spread. The findings suggest a new drug target that could lead to therapies for deadly metastatic skin cancer. When cancer cells colonize vital organs, they enter hostile territory, making it difficult to metastasize.
Melanoma cells, for instance, experience high levels of oxidative stress in the bloodstream and at distant sites that kill most metastasizing cells before they can form new tumors. But what enables cancer cells to escape the effects of oxidative stress and spread? A study, published Oct. 22 in Nature Cancer, details a mechanism that allows metastasizing melanoma cells to withstand this stress.
While the proteins in the body are usually constructed from 20 common amino acids, the researchers identified an enzyme called FTSJ1 that chemically tags the tRNA molecule carrying the 21st amino acid, selenocysteine. This modification called methlyation prompts the cancer cells to produce selenocysteine-containing proteins to cope with oxidative stress. "We dove into the unique biology of selenocysteine protein assembly and found a process that plays a central role in melanoma metastasis ," said senior author Dr.
Elena Piskounova, assistant professor of cell biology in dermatology at Weill Cornell Medicine. "Melanoma cells lacking the FTSJ1 enzyme are more sensitive to damaging oxidative stress, so developing therapies that tar.
