Skin Injury Promotes Healthy Cell Growth, Suppresses Cancer Formation

Healthy human skin is a mosaic-like collection of both normal and mutation-bearing cells. As people age, a growing number of these cells accumulate more and more mutations including those that can cause cancer. Eventually these mutant cells, which are fueled by environmental insults such as high sun exposure, gradually outcompete the healthy cells, making individuals increasingly susceptible to skin cancers.

But what happens to skin after it is injured? Do simple wounds or surgery increase skin cancer risks by expanding mutated cells, as some scientists believe? The surprising answer is no, according to a new study by researchers at Yale and the Karolinska Institute in Sweden. Rather than promoting mutant cell growth, they found, injury promotes healthy-cell expansion which in turn keeps mutated cell growth under control. The findings are published June 21 in the journal Nature.

By following the live behavior of cells in wounded and non-wounded skin and analyzing their respective molecular signals, the researchers found that injuries to skin activate a signaling cascade that favors healthy rather than mutated cells.

“This finding completely changes our way of thinking about cancer initiation and suggests that acute injury might actually counteract rather than promote tumorigenesis,” said lead author Sara Gallini, a research associate in the Greco Lab at the Yale School of Medicine (YSM).

The Greco Lab, which is led by Valentina Greco, the Carolyn Walch Slayman Professor of Genetics at YSM, conducted the research in collaboration with Kathleen Cook Suozzi, an associate professor at YSM, and Karl Annusver, a researcher in the lab of Maria Kasper, an associate professor at the Karolinska Institute and co-senior author of the study.

Researchers hope to design innovative therapeutics that combat cancer by stimulating cell signaling routes that enhance their selective proliferation of healthy cells and thereby suppress oncogenic growth, the authors said. Today’s cancer treatment strategies tend to suppress proliferative cells, a strategy that might inadvertently impair opportunities for mosaic tissue to deploy natural defenses against tumor cells, they added.

Reference: Gallini S, Annusver K, Rahman NT, et al. Injury prevents Ras mutant cell expansion in mosaic skin. Nature. 2023:1-9. doi: 10.1038/s41586-023-06198-y

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