fascin

Fascin is a family of actin-binding proteins that organize actin filaments into tight, parallel bundles. This activity promotes the formation of filopodia and other cellular protrusions and supports dynamic cell movement, shape changes, and adhesion. In humans, fascin is encoded by three genes: FSCN1 (fascin-1), FSCN2 (fascin-2), and FSCN3 (fascin-3); fascin-1 is the best characterized and is widely expressed in neurons, epithelial cells, and various migratory cells.

Biochemically, fascin binds along actin filaments to cross-link them into loose or tight bundles, increasing rigidity and enabling protrusive structures used in sensing and migration. The activity of fascin-1 is regulated by phosphorylation; phosphorylation of serine 39 by protein kinase C reduces actin-binding and bundling, while dephosphorylation enhances it. Other regulatory influences include cellular signaling pathways and interacting proteins.

Expression and role in disease: Fascin-1 is normally present at low levels in most adult tissues but is upregulated during development and in several cancers. High fascin-1 expression correlates with enhanced cell motility, invasion, and metastatic potential, and is associated with poorer prognosis in several tumor types. Conversely, reducing fascin-1 expression or blocking its bundling activity can impair invasion in cancer cell models.

Evolution and clinical considerations: Fascin is conserved among metazoans, with distinct paralogs in vertebrates. Because of its role in cell migration, fascin is studied as a potential biomarker and therapeutic target; inhibitors of fascin activity are under development to limit metastatic spread, though specificity and safety remain areas of investigation.