Lysophosphatidic acid regulates the motility of MCF10CA1a breast cancer cell sheets via two opposing signaling pathways.
Lysophosphatidic acid regulates the motility of MCF10CA1a breast cancer cell sheets via two opposing signaling pathways.
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DOI：
10.1016/j.cellsig.2018.01.005
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发表时间：
2018-05
影响因子：
4.8
通讯作者：
Parent CA
中科院分区：
文献类型：
--
作者：
Stuelten CH;Lee RM;Losert W;Parent CA
细胞的异常迁移导致了恶性细胞的扩散。无处不在的脂质介质溶血磷脂酸(LPA)调节细胞迁移，并与肿瘤进展有关。然而，调节LPA对细胞运动的影响的信号级联仍不清楚。利用时间推移成像和定量分析，我们研究了作用于LPA下游的信号级联对MCF10CA1a乳腺癌细胞运动的作用。我们发现LPA通过两条主要的信号通路改变细胞的运动性。Rho/ROCK信号通路是增加E-钙粘附素的细胞间黏附和肌动球蛋白的皮质排列以促进缓慢的、定向的、空间连贯的和时间一致的运动的主要途径。相反，GαI/o-和GαQ/11依赖的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源于Rho/ROCK和GαI/o-和GαQ/11依赖的通路的整合信号活性，从而允许对细胞或微环境的变化做出动态迁移反应。
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, Gαi/o- and Gαq/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 Gαi/o- and Gαq/11-dependent pathways, thus allowing for a dynamic migratory response to changes in the cellular or microenvironmental context.
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影响因子：
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