The Actin-Bundling Protein Fascin Stabilizes Actin in Invadopodia and Potentiates Protrusive Invasion

Research output: Contribution to journalArticle

Authors

  • A Li
  • JC Dawson
  • HJ Spence
  • X Yu
  • I Koenig
  • K Anderson
  • LM Machesky

Colleges, School and Institutes

Abstract

Fascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types. Fascin forms stable actin bundles with slow dissociation kinetics in vitro [1] and is regulated by phosphorylation of serine 39 by protein kinase C (PKC) [2]. Cancer cells use invasive finger-like protrusions termed invadopodia to invade into and degrade extracellular matrix. Invadopodia have highly dynamic actin that is assembled by both Arp2/3 complex and formins [3, 4]; they also contain components of membrane trafficking machinery such as dynamin and cortactin [5] and have been compared with focal adhesions and podosomes [6, 7]. We show that fascin is an integral component of invadopodia and that it is important for the stability of actin in invadopodia. The phosphorylation state of fascin at S39, a PKC site, contributes to its regulation at invadopodia. We further implicate fascin in invasive migration into collagen I-Matrigel gels and particularly in cell types that use an elongated mesenchymal type of motility in 3D. We provide a potential molecular mechanism for how fascin increases the invasiveness of cancer cells, and we compare invadopodia with invasive filopod-like structures in 3D.

Details

Original languageEnglish
Pages (from-to)339-345
Number of pages7
JournalCurrent Biology
Volume20
Issue number4
Publication statusPublished - 1 Feb 2010