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首页> 外文期刊>Oncogene >Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates
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Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates

机译:Rac和Rho信号参与3D基质中癌细胞的运动

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摘要

The motility of cancer cells in 3D matrices is of two types: mesenchymal motility, in which the cells are elongated and amoeboid motility, in which the cells are round. Amoeboid motility is driven by an actomyosin-based contractile force, which is regulated by the Rho/ROCK pathway. However, the molecular mechanisms underlying the motility of elongated cells remain unknown. Here, we show that the motility of elongated cells is regulated by Rac signaling through the WAVE2/Arp2/3-dependent formation of elongated pseudopodia and cell-substrate adhesion in 3D substrates. The involvement of Rac signaling in cell motility was different in cell lines that displayed an elongated morphology in 3D substrates. In U87MG glioblastoma cells, most of which exhibit mesenchymal motility, inhibition of Rac signaling blocked the invasion of these cells in 3D substrates. In HT1080 fibrosarcoma cells, which display mixed cell motility involving both elongated and rounded cells, inhibition of Rac1 signaling not only blocked mesenchymal motility but also caused a mesenchymal–amoeboid transition. Additionally, Rac1 and RhoA signaling regulated the mesenchymal and amoeboid motility in these cells, respectively, and the inhibition of both pathways dramatically decreased cell invasion. Hence, we could conclude that Rac1 and RhoA signaling simultaneously regulate cell invasion in 3D matrices.
机译:3D矩阵中癌细胞的运动性有两种:间充质运动(其中细胞呈细长形)和变形虫运动(其中细胞呈圆形)。 Amoeboid的运动性由基于肌动球蛋白的收缩力驱动,该收缩力受Rho / ROCK途径调控。然而,延长细胞运动的分子机制仍然是未知的。在这里,我们显示了细长细胞的运动性受到Rac信号的调控,该信号通过WAVE2 / Arp2 / 3依赖的细长假足和3D基质中细胞基质的粘附而形成。 Rac信号传导参与细胞运动的细胞系在3D基质中表现出拉长的形态。在U87MG胶质母细胞瘤细胞中,大多数表现出间质运动性,Rac信号的抑制作用阻止了这些细胞在3D基质中的侵袭。在HT1080纤维肉瘤细胞中,它表现出混合的细胞运动,包括伸长的细胞和圆形细胞,抑制Rac1信号不仅阻断了间充质运动,而且还引起了间充质-类胡萝卜素的转变。此外,Rac1和RhoA信号传导分别调节这些细胞的间充质和变形虫运动,并且两种途径的抑制作用均显着降低了细胞侵袭。因此,我们可以得出结论,Rac1和RhoA信号同时调节3D矩阵中的细胞侵袭。

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