Researchers discover what makes melanoma cells immortal

While scientists around the world pursue ways to extend the human healthspan, cancer cells have found a way to become immortal.

For the first time, researchers have discovered how one type of cancer – melanoma – achieves that immortality.

Unlike normal cells, cancer cells do not age and die. Instead, they somehow mutate and continue to multiply without end.

We have understood the general mutation process for years. In most cases, cancer cells become immortal by invoking a genetic mutation that triggers the production of the enzyme telomerase, which prevents telomeres from shortening. Telomeres prevent DNA-containing chromosomes from damage. The longer the telomere, the better protected the chromosome and the DNA within it. That means longer telomeres protect cancer cells.

But no one understood the specifics of how some cells mutate. Until now.

Scientists at the University of Pittsburgh School of Medicine have identified how melanoma tumor cells control their mortality. In a paper published in the journal “Science” the researchers explained how they discovered the combination of genetic alterations that skin cancer tumors use to promote explosive growth and prevent their own demise. 

The study reports that malignant melanocytes – melanin-producing cells in the skin – effectively become immortal in a two-step process that activates expressions of telomerase and a peptidase called tripeptidyl peptidase 1 (TPP1). Mutations in TPP1 and telomerase work together to lengthen the telomeres, preventing the normal process of replicative senescence, which allows cells to age and eventually die. Short telomeres are a sign of cellular aging, but extra-long telomeres are associated with cancer.

“There’s some special link between melanoma and telomere maintenance,” said Jonathan Alder, an assistant professor of medicine at the University of Pittsburgh School of Medicine, who is the senior author of the study, in an interview in Pittwire. “For a melanocyte to transform into cancer, one of the biggest hurdles is to immortalize itself. Once it can do that, it’s well on its way to cancer.”

Biochemists have long known that TPP1 increases the activity of telomerase in a test tube, but no one had demonstrated that it can occur clinically. When Alder’s team added mutated TERT and TPP1 back to cells, the two proteins worked together to create the distinctively long telomeres seen in melanoma tumors. TPP1 was the missing factor scientists had been searching for.

The Pittsburgh findings change how scientists think about the onset of melanoma. More importantly, they suggest there may be way to improve the cancer’s treatment by disrupting the process by which melanocytes become immortal.

We also hope the findings will be useful in the search for human longevity.