Data from: A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells

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.

转移性肿瘤细胞脱离原发肿瘤后，通过形成名为侵袭伪足（invadopodia）的富含肌动蛋白的膜突出结构进入血液循环，这类结构可降解细胞外基质，从而实现对周围组织的侵袭。侵袭伪足的形成受Rho GTP酶家族调控，该家族蛋白负责调控肌动蛋白细胞骨架。本研究揭示了RhoG在人类乳腺癌细胞中调控侵袭伪足解体的全新功能。研究结果显示，RhoG与Rac1在侵袭伪足动力学调控中发挥着相互独立且作用相反的功能。本研究同时证实，SGEF是侵袭伪足解体过程中负责激活RhoG的鸟苷酸交换因子。延时成像结果显示，与对照组细胞相比，RhoG及SGEF缺陷细胞中的侵袭伪足稳定性更强、存活寿命更长。此外，本研究结果表明，在侵袭伪足解体过程中发挥关键作用的桩蛋白（paxillin）的磷酸化水平，在RhoG缺陷细胞中显著受损。综上，本研究鉴定出一条由SGEF、RhoG及桩蛋白磷酸化组成的全新信号通路，该通路可调控乳腺癌细胞中侵袭伪足的解体过程。