Dynamic functions of RhoA in tumor cell migration and invasion

RhoA is one of the more extensively studied members of the Rho family of small GTPase where it is most readily recognized for its contributions to actin-myosin contractility and stress fiber formation. Accordingly, RhoA function during cell migration has been relegated to the rear of the cell where it mediates retraction of the trailing edge. However, RhoA can also mediate membrane ruffling, lamellae formation and membrane blebbing, thus suggesting an active role in membrane protrusions at the leading edge. With the advent of fluorescence resonance energy transfer (FRET)-based Rho activity reporters, RhoA has been shown to be active at the leading edge of migrating cells where it precedes Rac and Cdc42 activation. These observations demonstrate a remarkable versatility to RhoA signaling, but how RhoA function can switch between contraction and protrusion has remained an enigma. This review highlights recent advances regarding how the cooperation of Rho effector Rhotekin and S100A4 suppresses stress fiber generation to permit RhoA-mediated lamellae formation.