Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling
Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling
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DOI：
10.1242/jcs.067009
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发表时间：
2011-04-15
影响因子：
4
通讯作者：
Keely, Patricia J.
中科院分区：
文献类型：
--
作者：
Provenzano, Paolo P.;Keely, Patricia J.
细胞形状和扩散可以调节细胞增殖的概念已经发展了好几年，但直到最近才将其与细胞内部和细胞上的力量联系起来。事实证明，这一新兴的机械信号传导领域对于所有细胞类型来说都是广泛且重要的。细胞周围的微环境提供了一系列不同的、同时活跃的、生化的、结构的和机械的复杂刺激。在这种环境中，细胞通过拉动细胞外基质（ECM）和/或邻近细胞来探测其微环境的硬度。该过程依赖于跨细胞细胞-ECM 或细胞-细胞粘附，以及 Rho GTP 酶介导的细胞收缩性，以提供功能性连接，通过该功能性连接，力通过细胞内力生成蛋白通过细胞骨架传递。本评论涵盖了通过机械信号传导控制细胞增殖的基本机制的最新进展，重点是 3D 微环境和体内细胞外基质的作用。此外，由于最近人们对肿瘤-基质相互作用产生了很大的兴趣，我们将特别关注描述机械信号在乳腺癌进展中的作用的令人兴奋的新数据。
The notion that cell shape and spreading can regulate cell proliferation has evolved over several years, but only recently has this been linked to forces from within and upon the cell. This emerging area of mechanical signaling is proving to be wide-spread and important for all cell types. The microenvironment that surrounds cells provides a complex spectrum of different, simultaneously active, biochemical, structural and mechanical stimuli. In this milieu, cells probe the stiffness of their microenvironment by pulling on the extracellular matrix (ECM) and/or adjacent cells. This process is dependent on transcellular cell-ECM or cell-cell adhesions, as well as cell contractility mediated by Rho GTPases, to provide a functional linkage through which forces are transmitted through the cytoskeleton by intracellular force-generating proteins. This Commentary covers recent advances in the underlying mechanisms that control cell proliferation by mechanical signaling, with an emphasis on the role of 3D microenvironments and in vivo extracellular matrices. Moreover, as there is much recent interest in the tumor-stromal interaction, we will pay particular attention to exciting new data describing the role of mechanical signaling in the progression of breast cancer.