Department of Biological Sciences; Arkansas State University; State University, AR USA; Molecular Biosciences Program; Arkansas State University; State University, AR USA.
Department of Pharmacology; University of Pennsylvania Perelman School of Medicine; Philadelphia, PA USA.
Cell Adh Migr. 2014;8(1):55-9. doi: 10.4161/cam.27479. Epub 2013 Jan 1.
Cell migration is essential for a variety of fundamental biological processes such as embryonic development, wound healing, and immune response. Aberrant cell migration also underlies pathological conditions such as cancer metastasis, in which morphological transformation promotes spreading of cancer to new sites. Cell migration is driven by actin dynamics, which is the repeated cycling of monomeric actin (G-actin) into and out of filamentous actin (F-actin). CAP (Cyclase-associated protein, also called Srv2) is a conserved actin-regulatory protein, which is implicated in cell motility and the invasiveness of human cancers. It cooperates with another actin regulatory protein, cofilin, to accelerate actin dynamics. Hence, knockdown of CAP1 slows down actin filament turnover, which in most cells leads to reduced cell motility. However, depletion of CAP1 in HeLa cells, while causing reduction in dynamics, actually led to increased cell motility. The increases in motility are likely through activation of cell adhesion signals through an inside-out signaling. The potential to activate adhesion signaling competes with the negative effect of CAP1 depletion on actin dynamics, which would reduce cell migration. In this commentary, we provide a brief overview of the roles of mammalian CAP1 in cell migration, and highlight a likely mechanism underlying the activation of cell adhesion signaling and elevated motility caused by depletion of CAP1.
细胞迁移对于多种基本的生物学过程是必不可少的，如胚胎发育、伤口愈合和免疫反应。异常的细胞迁移也存在于病理条件下，如癌症转移，其中形态转化促进了癌症向新部位的扩散。细胞迁移是由肌动蛋白动力学驱动的，这是单体肌动蛋白（G-肌动蛋白）反复进出丝状肌动蛋白（F-肌动蛋白）的循环。CAP（环化酶相关蛋白，也称为 Srv2）是一种保守的肌动蛋白调节蛋白，它与细胞运动和人类癌症的侵袭性有关。它与另一种肌动蛋白调节蛋白肌动蛋白结合蛋白协同作用，加速肌动蛋白动力学。因此，CAP1 的敲低会减缓肌动蛋白丝的周转率，这在大多数细胞中会导致细胞迁移能力降低。然而，在 HeLa 细胞中耗尽 CAP1 会导致细胞运动性增加，尽管动力学减少。运动性的增加可能是通过细胞粘附信号的内向外信号转导激活的。激活粘附信号的潜力与 CAP1 耗竭对肌动蛋白动力学的负效应相竞争，这会降低细胞迁移。在这篇评论中，我们简要概述了哺乳动物 CAP1 在细胞迁移中的作用，并强调了 CAP1 耗竭激活细胞粘附信号和提高迁移率的可能机制。
