Lamb Maureen C, Tootle Tina L
Anatomy and Cell Biology Department, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Biology (Basel). 2020 Nov 17;9(11):403. doi: 10.3390/biology9110403.
Fascin, an actin-binding protein, regulates many developmental migrations and contributes to cancer metastasis. Specifically, Fascin promotes cell motility, invasion, and adhesion by forming filopodia and invadopodia through its canonical actin bundling function. In addition to bundling actin, Fascin has non-canonical roles in the cell that are thought to promote cell migration. These non-canonical functions include regulating the activity of other actin-binding proteins, binding to and regulating microtubules, mediating mechanotransduction to the nucleus via interaction with the Linker of the Nucleoskeleton and Cytoskeleton (LINC) Complex, and localizing to the nucleus to regulate nuclear actin, the nucleolus, and chromatin modifications. The many functions of Fascin must be coordinately regulated to control cell migration. While much remains to be learned about such mechanisms, Fascin is regulated by post-translational modifications, prostaglandin signaling, protein-protein interactions, and transcriptional means. Here, we review the structure of Fascin, the various functions of Fascin and how they contribute to cell migration, the mechanisms regulating Fascin, and how Fascin contributes to diseases, specifically cancer metastasis.
Fascin是一种肌动蛋白结合蛋白,它调控许多发育过程中的细胞迁移,并促进癌症转移。具体而言,Fascin通过其典型的肌动蛋白成束功能形成丝状伪足和侵袭性伪足,从而促进细胞运动、侵袭和黏附。除了使肌动蛋白成束外,Fascin在细胞中还具有非典型作用,这些作用被认为可促进细胞迁移。这些非典型功能包括调节其他肌动蛋白结合蛋白的活性、结合并调节微管、通过与核骨架和细胞骨架连接复合体(LINC复合体)相互作用介导向细胞核的机械转导,以及定位于细胞核以调节核肌动蛋白、核仁及染色质修饰。Fascin的多种功能必须得到协调调控才能控制细胞迁移。虽然关于此类机制仍有许多有待了解之处,但Fascin受翻译后修饰、前列腺素信号传导、蛋白质-蛋白质相互作用及转录方式的调控。在此,我们综述Fascin的结构、Fascin的各种功能及其如何促进细胞迁移、调控Fascin的机制,以及Fascin如何导致疾病,特别是癌症转移。