Hippo throws its weight behind migrating cells

Lucas et al. show that the Hippo pathway helps polarize actin so that groups of Drosophila cells can move in unison.

Cells often journey in packs during development and cancer metastasis. In the Drosophila ovary, a group of 4–8 border cells traverses the egg chamber and sidles up to the maturing egg. This maneuver requires adjustments by the actin cytoskeleton. Actin is more abundant and more dynamic at the outer edges of the cluster than in the interior, where the cells touch. The Hippo signaling pathway may help organize the actin cytoskeleton in these cells because it responds to polarity-inducing molecules and alters F-actin levels.

Lucas et al. found that members of the Hippo pathway gather at the interior membranes of the border cell cluster, putting them in position to shape cell polarity. Border cells that lack one protein in the pathway move slowly, the team discovered, and cells lacking two pathway members are even more sluggish or immobile.

The Hippo pathway targets the protein Ena, which spurs actin polymerization and formation of cell protrusions. Ena works by blocking capping proteins that thwart actin polymerization. In border cells, the presence of localized Hippo pathway components inhibits Ena at the inner membranes, unleashing capping proteins and damping actin dynamics in the interior of the clusters. In contrast, actin assembly continues at the outer edges of the cluster. Still uncertain, the researchers say, is whether Hippo promotes cell movement in other tissues and in cancer cells.