HAb18G/CD147 Promotes Cell Motility by Regulating Annexin II-Activated RhoA and Rac1 Signaling Pathways in Hepatocellular Carcinoma Cells
HAb18G/CD147 Promotes Cell Motility by Regulating Annexin II-Activated RhoA and Rac1 Signaling Pathways in Hepatocellular Carcinoma Cells
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HAb18G/CD147 通过调节肝细胞癌细胞中膜联蛋白 II 激活的 RhoA 和 Rac1 信号通路促进细胞运动
DOI：
10.1002/hep.24592
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发表时间：
2011-12-01
期刊：
影响因子：
13.5
通讯作者：
Chen, Zhi-Nan
中科院分区：
文献类型：
--
作者：
Zhao, Pu;Zhang, Wei;Chen, Zhi-Nan
肿瘤细胞可以以两种相互转换的方式作为单个细胞运动：间质模式和变形模式。细胞骨架重排在这种相互转化中起重要作用。以前，我们报道了HAb 18 G/CD 147和膜联蛋白II是参与细胞骨架重排的相互作用蛋白，但它们相互作用的作用尚不清楚。在这项研究中，我们发现，HAb 18 G/CD 147的消耗产生了圆形的形态，这是与变形虫运动，而膜联蛋白II的消耗导致在一个细长的形态，这是与间充质运动。HAb 18 G/CD 147的胞外部分可以与膜联蛋白II的磷酸化失活突变体相互作用并抑制其磷酸化。HAb 18 G/CD 147通过抑制膜联蛋白II磷酸化抑制Rho信号通路和变形样运动，通过整合素-FAK-PI 3 K/PIP 3信号通路促进WAVE 2和Rac 1活化的膜定位，并促进板状伪足的形成和间充质运动。结论：这些结果表明，HAb 18 G/CD 147与annexin II的相互作用参与了肝癌细胞间质和阿米巴样运动之间的相互转换。（肝脏学2011; 54：2012-2024）
Tumor cells can move as individual cells in two interconvertible modes: mesenchymal mode and amoeboid mode. Cytoskeleton rearrangement plays an important role in the interconversion. Previously, we reported that HAb18G/CD147 and annexin II are interacting proteins involved in cytoskeleton rearrangement, yet the role of their interaction is unclear. In this study we found that the depletion of HAb18G/CD147 produced a rounded morphology, which is associated with amoeboid movement, whereas the depletion of annexin II resulted in an elongated morphology, which is associated with mesenchymal movement. The extracellular portion of HAb18G/CD147 can interact with a phosphorylation-inactive mutant of annexin II and inhibit its phosphorylation. HAb18G/CD147 inhibits Rho signaling pathways and amoeboid movement by inhibiting annexin II phosphorylation, promotes membrane localization of WAVE2 and Rac1 activation by way of the integrin-FAK-PI3K/PIP3 signaling pathway, and promotes the formation of lamellipodia and mesenchymal movement. Conclusion: These results suggest that the interaction of HAb18G/CD147 with annexin II is involved in the interconversion between mesenchymal and amoeboid movement of hepatocellular carcinoma cells. (HEPATOLOGY 2011; 54: 2012-2024)