Cancer is so closely associated with DNA mutations that it seems almost inevitable that such changes must lead to cancer. But a square inch of skin can harbor tens of thousands of DNA changes and yet be tumor-free. How?
Cells, as it happens, aren’t passive victims of DNA damage. When faced with what could be cancer-causing DNA alterations, some cells sacrifice themselves. Others turn off their ability to divide. And there’s a third way, just discovered by scientists at Fred Hutchinson Cancer Research Center: they get specialized.
Skin is continually undergoing a cycle of shedding and creation of new skin. This process is sustained by skin stem cells, which balance two functions: creation of new specialized skin cells and renewal of themselves to ensure a never-ending source of new skin cells. In work published todayin Nature Cell Biology, Hutch researchers show that skin stem cells in mice respond to what ought to have been a cancer-causing mutation by opting to differentiate, or specialize, instead of renewing themselves. Because differentiated skin cells eventually slough off, the strategy appears to allow skin to jettison dangerous mutations without disrupting its function.
“We’ve been uncovering ways that tissues ensure their function and health long term, despite getting these [cancer-associated] mutations,” said senior author Dr. Slobodan Beronja, who studies the genes and molecular pathways that underlie cancer. The new mechanism the team discovered for preventing a mutated cell from becoming cancerous “just sort of nudges it gently out of the tissue using a physiological process of differentiation,” he said.
