Structure and role of WASP and WAVE in Rho GTPase signalling in cancer.

A major factor controlling the metastatic nature of cancer cells is their motility. Alterations in the signalling pathways controlling its regulation can lead to tumor cell invasion and metastasis. Directional motility involves protrusion of the cell's leading edge, via formation of filopodia and lamellipodia, adhesion to the substrate followed by tail retraction and de-adhesion. Rho GTPase binding proteins function as activators of the actin cytoskeleton and are key players in the transendothelial migration of cancer cells. Activation of the specific GTPases Rho, Rac1 and Cdc42 results in formation of actin stress fibres, membrane ruffles, lamellipodia and filopodia respectively and in cortical actin assembly. Pathways through which Rho GTPases elicit these effects are through direct interaction with members of the Wiskott-Alrich Syndrome Protein (WASP) family which stimulates structures such as lamellipodia and filopodia. The present review explores the role and function of Rho GTPases, WASP and WAVE in cancer metastasis.