Lo Vasco V R, Leopizzi M, Della Rocca C
Organi di Senso Department, Policlinico Umberto I, Faculty of Medicine and Dentistry, Sapienza University, viale del Policlinico 155, 00185, Rome, Italy,
J Cell Commun Signal. 2015 Mar;9(1):55-62. doi: 10.1007/s12079-015-0265-y. Epub 2015 Jan 25.
Selected Phosphoinositide-specific Phospholipase C (PI-PLC) enzymes occupy the convergence point of the broad range of pathways that promote Rho and Ras GTPase mediated signalling, which also regulate the activation of ezrin, a member of the ezrin-radixin-moesin (ERM) proteins family involved in the metastatic osteosarcoma spread. Previous studies described that in distinct human osteosarcoma cell lines ezrin networks the PI-PLC with complex interplay controlling the expression of the PLC genes, which codify for PI-PLC enzymes. In the present study, we analyzed the expression and the sub-cellular distribution of RhoA and Rac1 respectively after ezrin silencing and after PI-PLC ε silencing, in order to investigate whether ezrin-RhoGTPAses signalling might involve one or more specific PI-PLC isoforms in cultured 143B and Hs888 human osteosarcoma cell lines. In the present experiments, both ezrin and PLCE gene silencing had different effects upon RhoA and Rac1 expression and sub-cellular localization. Displacements of Ezrin and of RhoA localization were observed, probably playing functional roles.
选定的磷酸肌醇特异性磷脂酶C(PI-PLC)酶处于多种促进Rho和Ras GTPase介导信号传导途径的交汇点,这些信号传导途径还调节埃兹蛋白(ezrin)的激活,埃兹蛋白是埃兹蛋白-根蛋白-膜突蛋白(ERM)家族的成员,参与转移性骨肉瘤的扩散。先前的研究表明,在不同的人类骨肉瘤细胞系中,埃兹蛋白通过复杂的相互作用将PI-PLC连接起来,控制编码PI-PLC酶的PLC基因的表达。在本研究中,我们分别分析了埃兹蛋白沉默和PI-PLC ε沉默后RhoA和Rac1的表达及亚细胞分布,以研究在培养的143B和Hs888人骨肉瘤细胞系中,埃兹蛋白-RhoGTP酶信号传导是否可能涉及一种或多种特定的PI-PLC同工型。在本实验中,埃兹蛋白和PLCE基因沉默对RhoA和Rac1的表达及亚细胞定位均有不同影响。观察到埃兹蛋白和RhoA定位的改变,可能发挥着功能作用。