Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, PR China.
Hepatology. 2011 Dec;54(6):2012-24. doi: 10.1002/hep.24592.
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.
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.
肿瘤细胞可以以两种可转换的模式作为单个细胞移动：间质模式和阿米巴样模式。细胞骨架重排在相互转换中起着重要作用。以前，我们报道了 HAb18G/CD147 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 HAb18G/CD147 的耗竭产生了圆形形态，与阿米巴样运动相关，而膜联蛋白 II 的耗竭导致了伸长形态，与间质运动相关。HAb18G/CD147 的细胞外部分可以与膜联蛋白 II 的磷酸化非活性突变体相互作用并抑制其磷酸化。HAb18G/CD147 通过抑制膜联蛋白 II 的磷酸化抑制 Rho 信号通路和阿米巴样运动，通过整合素-FAK-PI3K/PIP3 信号通路促进 WAVE2 的膜定位和 Rac1 的激活，并促进片状伪足和间质运动的形成。
这些结果表明，HAb18G/CD147 与膜联蛋白 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转换。
