Di Jiehui, Huang Hui, Wang Yan, Qu Debao, Tang Juanjuan, Cheng Qian, Lu Zheng, Zhang Yanping, Zheng Junnian
Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China.
J Cancer Res Clin Oncol. 2015 Oct;141(10):1791-8. doi: 10.1007/s00432-015-1948-8. Epub 2015 Mar 12.
Cell migration requires spatiotemporal integration of signals that target cytoskeletal. Previous studies have indicated that Rho GTPases are crucial regulators of actin dynamics. As homologs of Rho proteins, the role of Rap2B in the regulation of cytoskeleton and its cell signaling pathway remains unknown.
The cellular functions of Rap2B were monitored by Western blotting and immunofluorescence staining in order to characterize the protein level and the cell shape.
Here, we show that expression of Rap2B was induced by nocodazole in a p53-dependent manner. However, Rap2B itself is not necessary for p53-dependent cell cycle arrest. We evidenced that over-expression of Rap2B may inhibit cell spreading by disrupting actin dynamics upon nocodazole treatment, but Rap2B (C180A) mutant does not. In contrast, knockdown of Rap2B promoted cell spreading.
Altogether, these results revealed that Rap2B plays a pivotal role in cytoskeleton reorganization and subsequently inhibits cell spreading, which could be responsible for cancer metastasis.
细胞迁移需要靶向细胞骨架的信号进行时空整合。先前的研究表明，Rho GTP酶是肌动蛋白动力学的关键调节因子。作为Rho蛋白的同源物，Rap2B在细胞骨架调节及其细胞信号通路中的作用尚不清楚。
通过蛋白质免疫印迹法和免疫荧光染色监测Rap2B的细胞功能，以表征蛋白质水平和细胞形态。
在此，我们表明诺考达唑以p53依赖的方式诱导Rap2B表达。然而，Rap2B本身对于p53依赖的细胞周期停滞并非必需。我们证明，Rap2B的过表达可能通过在诺考达唑处理时破坏肌动蛋白动力学来抑制细胞铺展，但Rap2B（C180A）突变体则不会。相反，敲低Rap2B可促进细胞铺展。
总之，这些结果表明Rap2B在细胞骨架重组中起关键作用，并随后抑制细胞铺展，这可能与癌症转移有关。
