Differential remodeling of actin cytoskeleton architecture by profilin isoforms leads to distinct effects on cell migration and invasion.
Differential remodeling of actin cytoskeleton architecture by profilin isoforms leads to distinct effects on cell migration and invasion.
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DOI：
10.1016/j.ccr.2012.09.027
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发表时间：
2012-11-13
期刊：
影响因子：
50.3
通讯作者：
Brugge JS
中科院分区：
文献类型：
--
作者：
Mouneimne G;Hansen SD;Selfors LM;Petrak L;Hickey MM;Gallegos LL;Simpson KJ;Lim J;Gertler FB;Hartwig JH;Mullins RD;Brugge JS
肌动蛋白细胞骨架的动态重组是细胞运动所必需的。Profilin是肌动蛋白聚合的调节因子；然而，共表达的Profilin异构体之间的功能差异还没有很好的定义。在这里，我们证明了profilin-1和profilin-2不同地调节膜的突起、运动和侵袭；这些过程被profilin-1促进，而被profilin-2抑制。与Profilin-1相比，Profilin-2通过EnA/Vasp蛋白EVL优先驱动肌动蛋白聚合。Profilin-2和EVL通过肌动球蛋白收缩依赖的机制抑制突起活动和细胞运动。重要的是，EVL或Profilin-2下调增强了体外和体内的侵袭。在人类乳腺癌中，EVL低表达与高侵袭性和不良患者预后相关。我们认为Profilin-2/EVL介导的肌动蛋白聚合增强了肌动蛋白的结合并抑制了乳腺癌细胞的侵袭。
Dynamic actin cytoskeletal reorganization is integral to cell motility. Profilins are well-characterized regulators of actin polymerization; however, functional differences among co-expressed profilin isoforms are not well defined. Here, we demonstrate that profilin-1 and profilin-2 differentially regulate membrane protrusion, motility, and invasion; these processes are promoted by profilin-1 and suppressed by profilin-2. Compared to profilin-1, profilin-2 preferentially drives actin polymerization by the Ena/VASP protein, EVL. Profilin-2 and EVL suppress protrusive activity and cell motility by an actomyosin contractility-dependent mechanism. Importantly, EVL or profilin-2 downregulation enhances invasion in vitro and in vivo. In human breast cancer, lower EVL expression correlates with high invasiveness and poor patient outcome. We propose that profilin-2/EVL-mediated actin polymerization enhances actin bundling and suppresses breast cancer cell invasion.
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影响因子：
64.5
作者：
Gertler, FB;Niebuhr, K;Soriano, P
通讯作者：
Soriano, P
口腔鳞状细胞癌中profilin 2表达的降低及其临床病理意义
影响因子：
4.2
作者：
Ma, C. Y.;Zhang, C. P.;Han, W.
通讯作者：
Han, W.
影响因子：
5.6
作者：
Kursula, Petri;Kursula, Inari;Wilmanns, Matthias
通讯作者：
Wilmanns, Matthias
DOI：
10.1083/jcb.201003014
发表时间：
2010-11-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hansen SD;Mullins RD
通讯作者：
Mullins RD
影响因子：
4.8
作者：
Lambrechts, A;Kwiatkowski, AV;Gertler, FB
通讯作者：
Gertler, FB