Fascin Regulates Nuclear Movement and Deformation in Migrating Cells

Dev Cell. 2016 Aug 22;38(4):371-83. doi: 10.1016/j.devcel.2016.07.021.


Fascin is an F-actin-bundling protein shown to stabilize filopodia and regulate adhesion dynamics in migrating cells, and its expression is correlated with poor prognosis and increased metastatic potential in a number of cancers. Here, we identified the nuclear envelope protein nesprin-2 as a binding partner for fascin in a range of cell types in vitro and in vivo. Nesprin-2 interacts with fascin through a direct, F-actin-independent interaction, and this binding is distinct and separable from a role for fascin within filopodia at the cell periphery. Moreover, disrupting the interaction between fascin and nesprin-2 C-terminal domain leads to specific defects in F-actin coupling to the nuclear envelope, nuclear movement, and the ability of cells to deform their nucleus to invade through confined spaces. Together, our results uncover a role for fascin that operates independently of filopodia assembly to promote efficient cell migration and invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Actins / metabolism
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Drosophila
  • HeLa Cells
  • Humans
  • Mice
  • Microfilament Proteins / metabolism*
  • Multiprotein Complexes / metabolism
  • Neoplasm Invasiveness / pathology
  • Neoplasms / pathology
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Envelope / metabolism
  • Nuclear Proteins / metabolism*
  • Protein Binding / physiology
  • Protein Structure, Tertiary
  • Pseudopodia / physiology*


  • Actins
  • Carrier Proteins
  • FSCN1 protein, human
  • Microfilament Proteins
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • SYNE2 protein, human