title: Loss of Scar/WAVE complex promotes N-WASP- and FAK-dependent invasion.
abstract: 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.
authors.affiliation: The Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Haoran
authors.initials: H
authors.lastname: Tang
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Bi
authors.forename: Douwe M
authors.initials: DM
authors.lastname: Veltman
authors.forename: Tobias
authors.initials: T
authors.lastname: Zech
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Spence
authors.forename: Xinzi
authors.initials: X
authors.lastname: Yu
authors.forename: Paul
authors.initials: P
authors.lastname: Timpson
authors.forename: Robert H
authors.initials: RH
authors.lastname: Insall
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Frame
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D051381:Rats; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; C114864:WASF1 protein, human; C495771:WASL protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human