PDF(Pubmed)
Abstract：
The actin 2/3 complex (Arp2/3) regulates actin polymerization and nucleation of actin filaments, is associated with cell motility, and has been shown to play a key role in the invasion and migration of cancer cells. nucleation-promoting factor (NPF) such as N-WASP (neural-WASP famly verprolin-homologous protein family), WAVE (WASP famly verprolin-homologous protein family), and WASH (WASP and Scar homologue) undergo conformational changes upon receipt of multiple upstream signals including Rho family GTPases, cdc42 (Cell division control protein 42 homolog), and phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5 P2) to bind and activate the Arp2/3 complex. Once activated, the Arp2/3 complex forms actin-based membrane protrusions necessary for cancer cells to acquire an invasive phenotype. Therefore, how to influence the invasion and migration of cancer cells by regulating the activity of the Arp2/3 complex has attracted great research interest in recent years. Several studies have explored the effects of phosphorylation modifications of cortactin and several NPFs (Nucleation Promoting Factor) including N-WASP and WAVE on the activity of the Arp2/3 complex and ultimately on cancer cell invasiveness, and have attempted to suggest new strategies for antiinvasive therapy as a result. Other studies have highlighted the potential of targeting genes encoding partial or complete proteins of the Arp2/3 complex as a therapeutic strategy to prevent cancer cell invasion and metastasis. This article reviews the role of the Arp2/3 complex in the development, invasion, and metastasis of different types of cancer and the mechanisms regulating the activity of the Arp2/3 complex.
摘要：
肌动蛋白2/3复合物（Arp2/3）调节肌动蛋白丝的聚合和成核，与细胞运动有关，并已被证明在癌细胞的侵袭和迁移中起关键作用。成核促进因子（NPF），如N-WASP（神经-WASP著名的verprolin同源蛋白家族），WAVE（WASP著名的维前列林同源蛋白家族），和WASH（WASP和疤痕同源物）在接收到包括Rho家族GTPases在内的多个上游信号时发生构象变化，cdc42（细胞分裂控制蛋白42同源物），和磷脂酰肌醇4,5-二磷酸（PtdIns4,5P2）结合并激活Arp2/3复合物。一旦激活,Arp2/3复合物形成癌细胞获得侵袭表型所必需的基于肌动蛋白的膜突起。因此,如何通过调控Arp2/3复合物的活性来影响癌细胞的侵袭和迁移,近年来引起了极大的研究兴趣。一些研究已经探索了皮质肌动蛋白和几种NPF（成核促进因子）（包括N-WASP和WAVE）的磷酸化修饰对Arp2/3复合物的活性以及最终对癌细胞侵袭的影响，并因此尝试提出新的抗侵入性治疗策略。其他研究强调了靶向编码Arp2/3复合物的部分或完整蛋白质的基因作为预防癌细胞侵袭和转移的治疗策略的潜力。本文回顾了Arp2/3复合物在发育中的作用，入侵,和不同类型癌症的转移以及调节Arp2/3复合物活性的机制。
