Loss of Scar/WAVE Complex Promotes N-WASP- and FAK-Dependent Invasion

Haoran Tang, Ang Li, Jing Bi, Douwe M. Veltman, Tobias Zech, Heather J. Spence, Xinzi Yu, Paul Timpson, Robert H. Insall, Margaret C. Frame, Laura M. Machesky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background
The Scar/WAVE regulatory complex (WRC) drives lamellipodia assembly via the Arp2/3 complex, whereas the Arp2/3 activator N-WASP is not essential for 2D migration but is increasingly implicated in 3D invasion. It is becoming ever more apparent that 2D and 3D migration utilize the actin cytoskeletal machinery differently.

Results
We discovered that WRC and N-WASP play opposing roles in 3D epithelial cell migration. WRC depletion promoted N-WASP/Arp2/3 complex activation and recruitment to leading invasive edges and increased invasion. WRC disruption also altered focal adhesion dynamics and drove FAK activation at leading invasive edges. We observed coalescence of focal adhesion components together with N-WASP and Arp2/3 complex at leading invasive edges in 3D. Unexpectedly, WRC disruption also promoted FAK-dependent cell transformation and tumor growth in vivo.

Conclusions
N-WASP has a crucial proinvasive role in driving Arp2/3 complex-mediated actin assembly in cooperation with FAK at invasive cell edges, but WRC depletion can promote 3D cell motility.

Original languageEnglish
Pages (from-to)107-117
Number of pages11
JournalCurrent Biology
Volume23
Issue number2
DOIs
Publication statusPublished - 21 Jan 2013

Keywords / Materials (for Non-textual outputs)

  • ACTIN
  • PATHWAYS
  • PROTEIN
  • DYNAMICS
  • WAVE REGULATORY COMPLEX
  • RAC ACTIVATION
  • MECHANISMS
  • DIFFERENTIATION
  • INVADOPODIA
  • FOCAL ADHESION KINASE

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