Rac and Rho GTPases in cancer cell motility control.
Rac and Rho GTPases in cancer cell motility control.
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DOI：
10.1186/1478-811x-8-23
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发表时间：
2010-09-07
期刊：
影响因子：
--
通讯作者：
Chiarugi P
中科院分区：
文献类型：
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作者：
Parri M;Chiarugi P
Rho GTP酶代表参与细胞骨架组织、迁移、转录和增殖的小GTP结合蛋白家族。这些过程的一个共同主题是肌动蛋白细胞骨架的动态重组，其现在已成为主要由Rho和Rac GTfl亚家族进行的主要开关控制，在细胞运动性对微环境的适应中发挥公认的作用。细胞在侵入3D环境时表现出三种不同的迁移模式.集体运动导致细胞群的运动，这些细胞群维持粘附连接并通过基质屏障的光解降解而运动。单细胞间质型运动的特征在于细长的细胞形状，并且再次需要细胞外蛋白水解和整合素接合。此外，它还依赖于Rac1介导的细胞极化和板状伪足的形成。相反，在变形虫运动中，细胞具有圆形形态，运动不依赖于蛋白酶，但需要高Rho GT3来驱动肌动球蛋白收缩性水平升高。这两种模式的细胞运动是相互转化的，几个移动的细胞，包括肿瘤细胞，表现出高度的可塑性，在运动风格之间的间充质或变形虫运动转移特设。这篇评论将集中在Rac和Rho小GTP酶在细胞运动中的作用，并在复杂的关系驱动Rac和Rho之间的相互控制授予侵略性癌细胞的机会主义运动行为。此外，我们分析了这些GTP酶在癌症进展和转移扩散中的作用。
Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. A common theme of these processes is a dynamic reorganization of actin cytoskeleton which has now emerged as a major switch control mainly carried out by Rho and Rac GTPase subfamilies, playing an acknowledged role in adaptation of cell motility to the microenvironment. Cells exhibit three distinct modes of migration when invading the 3 D environment. Collective motility leads to movement of cohorts of cells which maintain the adherens junctions and move by photolytic degradation of matrix barriers. Single cell mesenchymal-type movement is characterized by an elongated cellular shape and again requires extracellular proteolysis and integrin engagement. In addition it depends on Rac1-mediated cell polarization and lamellipodia formation. Conversely, in amoeboid movement cells have a rounded morphology, the movement is independent from proteases but requires high Rho GTPase to drive elevated levels of actomyosin contractility. These two modes of cell movement are interconvertible and several moving cells, including tumor cells, show an high degree of plasticity in motility styles shifting ad hoc between mesenchymal or amoeboid movements. This review will focus on the role of Rac and Rho small GTPases in cell motility and in the complex relationship driving the reciprocal control between Rac and Rho granting for the opportunistic motile behaviour of aggressive cancer cells. In addition we analyse the role of these GTPases in cancer progression and metastatic dissemination.