Throwing the Switch on Cancer

The most aggressively malignant cancer cells have a "toggle switch" that enables them to morph into highly mobile forms that invade other tissues and then nest comfortably in their new surroundings. This picture of how cancer cells shift between two alternating states—travelers and nesters—represents a new understanding of how cancer metastasizes, or spreads to other parts of the body, say researchers from Duke Comprehensive Cancer Center who conducted the study.

"Understanding this toggle switch might ultimately enable scientists to find ways to stop cells from metastasizing," says the study's lead investigator, Mariano Garcia-Blanco, professor of molecular genetics and microbiology.

Until now, scientists have believed that cancer cells must transform permanently from stationary "epithelial" cells into migratory "mesenchymal" cells in order to metastasize. The Duke team discovered that highly malignant cells are equal parts epithelial and mesenchymal, transitioning between the two as their surroundings necessitate. The proteins that the cell produces dictate which way the cell shifts.

In a classic example of survival of the fittest, a cancer cell's ability to toggle between epithelial and mesenchymal enables the most malignant cells to aggressively invade and then peacefully adapt in unfamiliar territory, the scientists report. They published their findings in the journal Proceedings of the National Academy of Sciences.

The team's next step is to determine precisely what controls the toggle mechanism in cancer cells, Garcia-Blanco says. Identifying the various steps that occur during the natural progression of tumors could lead to therapies for blocking metastasis.