How skin cells cooperate to thwart cancer

Melanoma is a life-threatening skin cancer that spreads quickly to other organs if not treated early. A new discovery by University of California, Irvine biologists shatters traditional beliefs about how melanomas develop, providing new insights into fighting the disease. The scientists’ research appears in eLife.

Arthur Lander, the Donald Bren Professor of development & cell biology, and his colleagues investigated melanocytic nevi, colloquially known as common pigmented moles. Adults typically develop dozens of them throughout their lives. They generally remain benign, but not always.

“At the molecular level, virtually all of these moles carry a mutation that is one of the most frequent for melanoma,” Lander said. “However, moles almost always stop growing before a second mutation can push them in the direction of becoming cancerous. It’s when the growth process doesn’t halt that melanoma can result.”

Until now, scientists have thought that moles stop growing because stress from the original mutation prematurely ages them. The UCI team’s findings overturn that idea.

“What we found points to a new understanding, which is that moles shut down because the cells inside them communicate with each other,” said Lander, adding they probably do so by sending out signals in the form of proteins. “When the moles get to a certain size, this communication becomes strong enough that their cells collectively stop growing. In fact, many tissues control their sizes in much this way.”

Rolando Ruiz-Vega, a postdoctoral scholar in development & cell biology nd the paper’s first author, said: “When scientists talk about fighting cancer, they are often referring to developing drugs to target a particular mutation. However, we see here that the specific mutation isn’t really what controls whether cancer happens or not. Cells are telling, or not telling, each other to stop growing.”

The discovery could lead to new ways to treat melanomas, or even prevent them by devising mechanisms to stop moles from turning into cancer.

“We would like to more precisely identify what signals the cells are sending and determine how to tell when moles are transitioning from normal to malignant,” said Lander. “If we can spot this early on and stop the process, it would be a huge leap forward.”

The research was a collaboration between the laboratories of Lander and Anand Ganesan, a professor of dermatology and biological chemistry, with assistance from John Lowengrub, a Chancellor’s Professor of mathematics.

The work was funded through National Cancer Institute support for the UCI Center for Cancer Systems Biology; the National Institute of Biomedical Imaging and Bioengineering; the University of California; and the National Academies of Sciences, Engineering and Medicine.

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