Melanoma Maneuvers Mortality by Maintaining Telomeres
Source: Genetic Engineering & Biotechnology News, November 2022
It may appear counter-intuitive but overcoming death is a key step in the journey of a cell toward cancer.
A study published in the journal Science shows malignant melanocytes—melanin-producing cells in the skin—accomplish this feat in two conspiring steps that activate expressions of telomerase and a peptidase called tripeptidyl peptidase 1 (TPP1). Mutations in TPP1 and telomerase synergistically lengthen the protective caps at chromosomal ends (telomeres), preventing the normal process of replicative senescence which allows cells to age with every cycle of replication and eventually die due to shortened telomeres. 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, PhD, an assistant professor of medicine at the University of Pittsburgh School of Medicine, who is the senior author of the study. “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.”
Identifying the exact combination of mutations in melanoma that prevents death and achieves explosive, indefinite growth could change the way clinicians understand and treat melanoma.