When a cancer cell hangs a left, it needs the protein cofilin. As Sidani et al. report, cofilin helps wandering cancer cells change course by enabling them to turn.
Cofilin is important for cells on the go. As a cell crawls, actin fibers at its front edge polymerize, pushing the membrane forward. Cofilin promotes the elongation of these fibers by breaking them: the fresh ends double the number of attachment points for other actin segments and lure the Arp2/3 complex, which hops on and extends the fibers. Although researchers have worked out some of cofilin's functions, they didn't have a comprehensive picture of how the protein influences cell movement.
Sidani et al. knocked out the protein in a line of aggressive mouse mammary tumor cells. Instead of moving in random directions, the cells crawled straight ahead, rarely turning. The knockout cells sent out fewer lamellipodia, the extensions they use to probe their environment, and the lamellipodia they did produce were stickier, thus inhibiting course changes.
By breaking actin fibers, cofilin draws the Arp2/3 complex to different locations at the cell edge. New lamellipodia sprout at these spots, and the cell shifts direction. Without cofilin, Arp2/3 piles up at the front of the cell, which only goes forward. The researchers have already shown that quashing cofilin activity leashed wandering tumor cells, suggesting that cofilin-blocking drugs will do the same.