A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells
A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells
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DOI：
10.1242/jcs.195552
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发表时间：
2017-03-15
影响因子：
4
通讯作者：
Garcia-Mata, Rafael
中科院分区：
文献类型：
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作者：
Goicoechea, Silvia M.;Zinn, Ashtyn;Garcia-Mata, Rafael
癌症的标志之一是肿瘤细胞侵入周围组织并转移的能力。在转移过程中，癌细胞降解细胞外基质，细胞外基质作为一个物理屏障，通过发展专门的富含肌动蛋白的膜突起结构称为侵袭伪足。侵袭伪足的形成受Rho GTP酶（调节肌动蛋白细胞骨架的蛋白质家族）调节。在这里，我们描述了一个新的作用，RhoG在人类乳腺癌细胞的侵袭伪足拆卸的调节。我们的研究结果表明，RhoG和Rac1具有独立的和相反的作用，在invadopodia动态的调节。我们还表明，SGEF（也被称为ARHGEF26）是负责激活RhoG在入侵伪足拆卸的交换因子。当RhoG或SGEF的表达被沉默时，侵袭伪足比对照细胞更稳定并且具有更长的寿命。我们的研究结果还表明，RhoG和SGEF调节桩蛋白的磷酸化，桩蛋白在侵入伪足拆卸过程中起着关键作用。总之，我们已经确定了一种新的信号通路，涉及SGEF，RhoG和桩蛋白磷酸化，其功能在乳腺癌细胞中的侵袭伪足拆卸的调节。
One of the hallmarks of cancer is the ability of tumor cells to invade surrounding tissues and metastasize. During metastasis, cancer cells degrade the extracellular matrix, which acts as a physical barrier, by developing specialized actin-rich membrane protrusion structures called invadopodia. 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 (also known as ARHGEF26) is the exchange factor responsible for the activation of RhoG during invadopodia disassembly. When the expression of either RhoG or SGEF is silenced, invadopodia are more stable and have a longer lifetime than in control cells. Our findings also demonstrate that RhoG and SGEF modulate the phosphorylation of paxillin, which plays a key role during invadopodia disassembly. 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.