Rho蛋白与细胞骨架调节的细胞运动

Rho Protein and Cell Movement Regulated by Cytoskeleton CAO Wenfeng, SUN Baocun

细胞迁移是肿瘤细胞浸润和转移的关键环节,细胞骨架的重组过程是细胞发生移动的基础,受多种信号分子的调节。肿瘤细胞可以表现出多种类型的运动方式,而每种细胞运动方式可由不同的分子机制调节,其中细胞骨架蛋白actin的重组在肿瘤细胞的运动中至关重要。Rho蛋白家族的小GTP酶蛋白在肿瘤细胞中被活化,可以通过调节细胞骨架actin的重组,引起细胞侵袭、转移。其活化方式包括:Rho蛋白及其调节子的活化突变、灭活突变和Rho家族蛋白和作用分子表达水平的改变等,通过自身活化将细胞外的趋化信号传递给细胞内的下游效应分子,导致细胞骨架依赖性的反应,影响细胞的移动功能。因而,对Rho家族的小GTP酶蛋白信号进行有效的抑制可以有效的抑制肿瘤细胞的侵袭和转移过程,是肿瘤治疗的新方法。

Cell migration is the key step in cancer invasion and metastasis, and the basis of it is the reorganization of cytoskeleton protein, which can be regulated by several signal molecules. Cancer cells may show several movement patterns, which can be controlled by different molecular mechanisms among which the process of the reorganization of cytoskeleton actin protein may be very important. Rho family small GT- Pases can be activated and then regulate the reorganization of cytoskeleton actin, thus can cause cancer cell invasion and metastasis. The activation pathway includes activated mutation （RhoH is the main target of activated mutation in Rho family, which is related with lymphoma） and inactivated mutation of Rho protein and its regulon （p190RhoGAP can down-regulate Rho activity, acting as cancer inhibitor in gliomas）. The alteration of expression level of Rho protein and molecule （Rho protein family has 3 Rho monomers including RhoA, RhoB, and RhoC and 3 Rac monomers including Racl, Rac2, and Rac3. RhoC mRNA up-expression suggests the metastasis of melanoma.） can transform chemo-attractant signals from extra cell to downstream effector molecule intra cell, then make the reaction to cytoskeleton dependence and affect cell migration （Mesenchymal-like cell motility is associated with Rac-dependent and F-actin-rich protrusions and does not require Rho and ROCK, but the amoeboid mode of invasion shows the dependence of ROCK-mediated actin cytoskeletal dynamics on the increased capacity of cells to generate force.）. Therefore, inhibition of the signal transduction of Rho family small GTPases can efficiently restrain the cancer invasion and metastasis and may be another novel candidate method for cancer therapy.