The type III TGFbeta receptor regulates directional migration: new tricks for an old dog.

The type III transforming growth factor beta (TGFbeta) receptor (T beta RIII or betaglycan) is a TGFbeta superfamily co-receptor. Loss of T beta RIII expression occurs in a broad spectrum of human cancers including cancers of the breast, kidney, lung, ovary, pancreas and prostate. T beta RIII suppresses cancer progression, in part, by reducing cancer cell motility. This T beta RIII function is independent of its TGFbeta signaling role, with T beta RIII activating Cdc42 via its interaction with the scaffolding protein beta-arrestin2 to re-organize the actin cytoskeleton, decrease directional persistence and inhibit random migration in both epithelial-derived cancer cells and normal epithelial cells. These studies contribute to a growing body of literature supporting essential and non-redundant roles for T beta RIII and emphasize the importance of continued investigation of T beta RIII and other signaling co-receptors.