Metastatic cells escape the primary tumor and enter the bloodstream by developing actin-rich membrane protrusions called invadopodia that degrade the extracellular matrix to allow invasion of surrounding tissues. The formation of invadopodia is regulated by Rho GTPases, a family of proteins that regulates the actin cytoskeleton. Here, we describe a novel role for RhoG in the regulation of invadopodia disassembly in human breast cancer cells. Our results show that RhoG and Rac1 have independent and opposite roles in the regulation of invadopodia dynamics. We also show that SGEF is the exchange factor responsible for the activation of RhoG during invadopodia disassembly. Time-lapse imaging shows that invadopodia in RhoG- and SGEF-deficient cells are more stable and have a longer lifetime than in control cells. Moreover, our findings demonstrate that phosphorylation of paxillin, which plays a key role during invadopodia disassembly, is markedly impaired in RhoG deficient cells. In summary, we have identified a novel signaling pathway involving SGEF, RhoG, and paxillin phosphorylation, which functions in the regulation of invadopodia disassembly in breast cancer cells.
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