Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6.
Collective cell migration requires suppression of actomyosin at cell-cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6.
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DOI：
10.1038/ncb2133
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发表时间：
2011-01
影响因子：
21.3
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中科院分区：
文献类型：
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集体细胞迁移发生在一系列情况下：癌细胞经常侵入队列，同时保留细胞-细胞连接。在这里，我们表明，集体癌细胞的侵袭依赖于减少肌动球蛋白的收缩性在网站的细胞接触。当肌动球蛋白在细胞-细胞接触处没有下调时，迁移细胞失去凝聚力。我们为这种下调提供了一种新的分子机制。盘状结构域受体1（DDR 1）的消耗在一系列2D、3D和“器官型”模型中阻断了集体癌细胞侵袭。DDR 1通过其C末端结合Par 3和Par 6中的PDZ结构域协调Par 3/6细胞极性复合物。DDR 1/Par 3/6复合物控制RhoE定位于细胞-细胞接触，在细胞-细胞接触中它拮抗ROCK驱动的肌动球蛋白收缩性。DDR 1、Par 3、Par 6或RhoE的消耗导致细胞-细胞接触处的肌动球蛋白增加，细胞-细胞凝聚力丧失和有缺陷的集体细胞侵袭。
Collective cell migration occurs in a range of contexts: cancer cells frequently invade in cohorts while retaining cell-cell junctions. Here we show that collective cancer cell invasion depends on reducing actomyosin contractility at sites of cell-cell contact. When actomyosin is not down-regulated at cell-cell contacts migrating cells lose cohesion. We provide a novel molecular mechanism for this down-regulation. Depletion of Discoidin Domain Receptor 1 (DDR1) blocks collective cancer cell invasion in a range of 2D, 3D and ‘organotypic’ models. DDR1 co-ordinates the Par3/6 cell polarity complex through its C-terminus binding PDZ domains in Par3 and Par6. The DDR1/Par3/6 complex controls the localisation of RhoE to cell-cell contacts where it antagonizes ROCK-driven actomyosin contractility. Depletion of DDR1, Par3, Par6 or RhoE leads to increased actomyosin at cell-cell contacts, a loss of cell-cell cohesion and defective collective cell invasion.