fascin1

Fascin-1, or fascin actin-bundling protein 1, is a cytoskeletal protein encoded by the FSCN1 gene in humans. It cross-links actin filaments into tight, parallel bundles that support the formation of filopodia and other cellular protrusions essential for directional cell migration. By organizing actin filaments into rigid bundles, fascin-1 helps generate the protrusive structures used by migrating cells.

Structurally, fascin-1 is a monomeric protein comprising four beta-trefoil domains. It binds actin filaments at multiple sites, enabling the formation and stabilization of parallel actin bundles. In cells, fascin-1 localizes to filopodial tips and other dynamic actin-rich regions, where it promotes protrusive activity and mobility.

Fascin-1 activity is regulated by phosphorylation and cellular signaling. Phosphorylation by protein kinase C at Ser39 reduces actin-bundling activity, while dephosphorylation enhances bundling. Expression of fascin-1 is prominent in migrating cells and certain neuronal and immune cell types, and there are related fascin family members (FSCN2 and FSCN3) with tissue-specific expression.

Clinical relevance is primarily linked to cancer biology. FSCN1 overexpression has been associated with increased invasion and metastasis in several cancers, including breast, colorectal, and glioma, and it can correlate with poorer prognosis in some patient cohorts. Because of its role in metastasis, fascin-1 is studied as a potential biomarker and therapeutic target. Preclinical research has explored small-molecule inhibitors and other strategies aimed at disrupting fascin-1–mediated actin bundling to impair tumor cell migration.