Cancer cells form actin-rich adhesive structures called invadopodia, which allow invasion and degradation of the extracellular matrix (ECM). Several adhesion proteins relocalise to forming invadopodia, which also assemble actin- and cortactin-rich punctae. It has been described that the multifunctional family of Rho GTPases control invadopodia formation, but the exact underlying mechanisms are unknown. Now, on page 1064, Rafael Garcia-Mata and colleagues address the role of the Rac-related RhoG protein in the regulation of invadopodia disassembly in human breast cancer cells. Knockdown of RhoG results in an increase in invadopodia formation, whereas its overexpression reduces the number of cells with invadopodia. Furthermore, the guanine-nucleotide-exchange factor SGEF is found to function upstream of RhoG in invadopodia formation, and both SGEF and RhoG regulate the phosphorylation levels of the adhesion protein paxillin to control invadopodia disassembly. However, despite increased invadopodia formation upon deletion of RhoG and SGEF, the ability of these cells to invade the ECM is impaired, suggesting that enhanced formation of invadopodia is not sufficient for invasion. Interestingly, RhoG and its downstream effector Rac1 play opposing roles and function independently in invadopodia formation, with Rac1 involved in invadopodia assembly and RhoG during disassembly. Thus, the results presented here contribute to the understanding of the roles of Rho GTPases in invadopodia dynamics and breast cancer invasion.
- © 2017. Published by The Company of Biologists Ltd