CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion
CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion
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DOI：
10.1083/jcb.201912159
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发表时间：
2020-09-07
影响因子：
7.8
通讯作者：
Calvo, Fernando
中科院分区：
文献类型：
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作者：
Farrugia, Aaron J.;Rodriguez, Javier;Calvo, Fernando
快速的阿米巴迁移对发育过程至关重要，并可被癌细胞劫持以促进转移扩散。这种迁移行为受到高水平的肌动蛋白收缩的严格控制，但它是如何与其他细胞骨架成分耦合的却知之甚少。Septins作为一种新的细胞骨架成分越来越受到人们的重视，但关于它们的调控和对迁移的贡献的细节尚不清楚。在这里，我们发现，阿米巴黑色素瘤细胞侵袭和迁移到富含胶原蛋白的基质中，以及在体内局部侵袭和扩散，始终需要Septin调节剂CDC42EP5。CDC42EP5与肌动蛋白结构相关，导致肌动蛋白收缩能力增强和阿米巴迁移。CDC42EP5通过SEPT9依赖的F-肌动蛋白交联来影响这些功能，这使得高收缩肌球蛋白结构持续稳定所需的F-肌动蛋白束的产生成为可能。这项研究提供的证据表明，CDC42EP5是癌细胞运动的调节器，协调肌动蛋白和Septin网络，并描述了SEPT9在黑色素瘤侵袭和转移中的独特作用。
Fast amoeboid migration is critical for developmental processes and can be hijacked by cancer cells to enhance metastatic dissemination. This migratory behavior is tightly controlled by high levels of actomyosin contractility, but how it is coupled to other cytoskeletal components is poorly understood. Septins are increasingly recognized as novel cytoskeletal components, but details on their regulation and contribution to migration are lacking. Here, we show that the septin regulator Cdc42EP5 is consistently required for amoeboid melanoma cells to invade and migrate into collagen-rich matrices and locally invade and disseminate in vivo. Cdc42EP5 associates with actin structures, leading to increased actomyosin contractility and amoeboid migration. Cdc42EP5 affects these functions through SEPT9-dependent F-actin cross-linking, which enables the generation of F-actin bundles required for the sustained stabilization of highly contractile actomyosin structures. This study provides evidence that Cdc42EP5 is a regulator of cancer cell motility that coordinates actin and septin networks and describes a unique role for SEPT9 in melanoma invasion and metastasis.