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

Li, A., Dawson, J. C., Forero-Vargas, M., Spence, H. J., Yu, X., König, I., Anderson, K. and Machesky, L. M. (2010) The Actin-Bundling Protein Fascin Stabilizes Actin in Invadopodia and Potentiates Protrusive Invasion. Current Biology, 20(4), pp. 339-345. (doi: 10.1016/j.cub.2009.12.035) (PMID:20137952) (PMCID:PMC3163294)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Anderson, Professor Kurt and Yu, Dr Xinzi and Dawson, Dr John and Spence, Dr Heather and Li, Mr Ang and Machesky, Professor Laura
• Authors: Li, A., Dawson, J. C., Forero-Vargas, M., Spence, H. J., Yu, X., König, I., Anderson, K., and Machesky, L. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Current Biology
• Publisher: Elsevier (Cell Press)
• ISSN: 0960-9822
• ISSN (Online): 1879-0445
• Published Online: 04 February 2010