Aberrant cell migration leads to the dispersal of malignant cells. The ubiquitous lipid mediator lysophosphatidic acid (LPA) modulates cell migration and is implicated in tumor progression. Yet, the signaling cascades that regulate LPA's effect on cell motility remain unclear. Using time-lapse imaging and quantitative analyses, we studied the role of signaling cascades that act downstream of LPA on the motility of MCF10CA1a breast cancer cells. We found that LPA alters cell motility via two major signaling pathways. The Rho/ROCK signaling cascade is the predominant pathway that increases E-Cadherin containing cell–cell adhesions and cortical arrangement of actomyosin to promote slow, directional, spatially coherent and temporally consistent movement. In contrast, Gα_i/o- and Gα_q/11-dependent signaling cascades lessen directionality and support the independent movement of cells. The net effect of LPA on breast cancer cell migration therefore results from the integrated signaling activity of the Rho/ROCK and Gα_i/o- and Gα_q/11-dependent pathways, thus allowing for a dynamic migratory response to changes in the cellular or microenvironmental context.

异常细胞迁移导致恶性细胞的扩散。普遍存在的脂质介质溶血磷脂酸 (LPA) 调节细胞迁移并参与肿瘤进展。然而，调节 LPA 对细胞运动影响的信号级联仍不清楚。使用延时成像和定量分析，我们研究了 LPA 下游信号级联对 MCF10CA1a 乳腺癌细胞运动的作用。我们发现 LPA 通过两条主要信号通路改变细胞运动。 Rho/ROCK 信号级联是增加含有 E-钙粘蛋白的细胞间粘附和肌动球蛋白皮质排列的主要途径，以促进缓慢、定向、空间连贯和时间一致的运动。相反，Gα _i/o和 Gα _q/11依赖性信号级联减弱了方向性并支持细胞的独立运动。因此，LPA 对乳腺癌细胞迁移的净效应是由 Rho/ROCK 和 Gα _i/o和 Gα _q/11依赖性途径的整合信号传导活性产生的，从而允许对细胞或细胞的变化做出动态迁移反应。微观环境背景。