文章：

为入侵而成核的肌动蛋白

Nucleating actin for invasion

原文发布日期：2011-02-10

DOI: 10.1038/nrc3003

类型: Review Article

开放获取: 否

要点：

1. Actin polymerization inside cells is initiated by actin nucleation factors. Reassembly of the actin cytoskeleton is essential for invasive cell migration. Understanding the specific mechanisms of action and regulation of the diverse and growing number of actin nucleators is likely to provide new ideas for developing treatments that inhibit cancer spread and inflammatory conditions.
2. Actin nucleators such as formins or the Arp2/3 complex and nucleation-promoting factors have numerous and diverse functions in invasive cancer cell migration, including the formation of protrusive structures, assembly of cell–cell contacts and matrix degradation. In addition, they have been implicated in the regulation of proinvasive signalling pathways.
3. There is now a large body of clinical evidence for specific roles of actin nucleators in cancer progression. Importantly, many of these factors seem to be associated with advanced disease and the metastatic spread of human cancers.
4. Actin nucleation factors now emerge as promising targets for therapeutic intervention in metastatic and invasive or inflammatory diseases. The first small-molecule inhibitors of actin nucleators have been reported very recently.

要点翻译：

1. 细胞内的肌动蛋白聚合由肌动蛋白成核因子启动。肌动蛋白细胞骨架的重组对于侵袭性细胞迁移至关重要。理解日益多样化的肌动蛋白成核因子的具体作用机制和调控方式，有望为开发抑制癌症扩散和炎症性疾病的治疗方法提供新思路。
2. 诸如形成素或Arp2/3复合物等肌动蛋白成核因子及其促核因子在侵袭性癌细胞迁移中具有众多多样化功能，包括突起结构的形成、细胞间接触点的组装以及基质降解。此外，它们还参与调控促侵袭信号通路。
3. 目前已有大量临床证据表明肌动蛋白成核因子在癌症进展中发挥特定作用。重要的是，许多这类因子似乎与晚期疾病及人类癌症的转移扩散密切相关。
4. 肌动蛋白成核因子现已成为治疗转移性、侵袭性或炎症性疾病的有前景靶点。首批肌动蛋白成核因子的小分子抑制剂已于近期成功研发。

英文摘要：

The invasion of cancer cells into the surrounding tissue is a prerequisite and initial step in metastasis, which is the leading cause of death from cancer. Invasive cell migration requires the formation of various structures, such as invadopodia and pseudopodia, which require actin assembly that is regulated by specialized actin nucleation factors. There is a large variety of different actin nucleators in human cells, such as formins, spire and Arp2/3-regulating proteins, and the list is likely to grow. Studies of the mechanisms of various actin nucleation factors that are involved in cancer cell function may ultimately provide new treatments for invasive and metastatic disease.

摘要翻译： 

癌细胞侵入周围组织是转移的前提和初始步骤，而转移是癌症导致死亡的主要原因。侵袭性细胞迁移需要形成各种结构，如侵袭足和伪足，这些结构的形成需要由特定肌动蛋白成核因子调控的肌动蛋白组装。人类细胞中存在多种不同的肌动蛋白成核因子，如formin家族、spire蛋白以及Arp2/3调节蛋白，且这一列表可能还会继续增加。研究参与癌细胞功能的各种肌动蛋白成核因子机制，最终可能为侵袭性和转移性疾病提供新的治疗方法。

原文链接：

Nucleating actin for invasion