A factor that promotes the formation and maintenance of pigmented birthmarks called giant congenital naevi, and subsequently of melanoma, is reported online this week in Nature Cell Biology. These findings could provide important insights for the development of therapeutic strategies for this condition.
Olga Shakhova, Lukas Sommer and colleagues used a mouse model of melanoma that combined the presence of mutant Nras, a known melanoma-promoting factor, and deficiency of INK4a, which is often inactivated in human melanoma. The authors identified striking similarities between this mouse model and giant congenital naevi and melanoma in humans. They went on to show that Sox10, a factor needed for the formation of skin pigment cells from neural crest stem cells during development, was present at high levels in naevi and melanoma samples obtained from both the mouse model and human patients. The authors further demonstrated that a decrease in Sox10 levels counteracted melanoma formation in mice by suppressing neural crest stem cell properties, and by blocking cell proliferation and survival.
The finding that Sox10 is crucial for the formation and maintenance of giant congenital naevi and melanoma has the potential to be exploited therapeutically against this aggressive skin cancer.