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

doi:10.1016/j.cub.2012.11.059

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 journal › Article › peer-review

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.

Original language	English
Pages (from-to)	107-117
Number of pages	11
Journal	Current Biology
Volume	23
Issue number	2
DOIs	https://doi.org/10.1016/j.cub.2012.11.059
Publication status	Published - 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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10.1016/j.cub.2012.11.059

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@article{017dde1a3b164df68b2277f1f32a176b,

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.",

keywords = "ACTIN, PATHWAYS, PROTEIN, DYNAMICS, WAVE REGULATORY COMPLEX, RAC ACTIVATION, MECHANISMS, DIFFERENTIATION, INVADOPODIA, FOCAL ADHESION KINASE",

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

year = "2013",

month = jan,

day = "21",

doi = "10.1016/j.cub.2012.11.059",

language = "English",

volume = "23",

pages = "107--117",

journal = "Current Biology",

issn = "0960-9822",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - Loss of Scar/WAVE Complex Promotes N-WASP- and FAK-Dependent Invasion

AU - Tang, Haoran

AU - Li, Ang

AU - Bi, Jing

AU - Veltman, Douwe M.

AU - Zech, Tobias

AU - Spence, Heather J.

AU - Yu, Xinzi

AU - Timpson, Paul

AU - Insall, Robert H.

AU - Frame, Margaret C.

AU - Machesky, Laura M.

PY - 2013/1/21

Y1 - 2013/1/21

N2 - 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.

AB - 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.

KW - ACTIN

KW - PATHWAYS

KW - PROTEIN

KW - DYNAMICS

KW - WAVE REGULATORY COMPLEX

KW - RAC ACTIVATION

KW - MECHANISMS

KW - DIFFERENTIATION

KW - INVADOPODIA

KW - FOCAL ADHESION KINASE

U2 - 10.1016/j.cub.2012.11.059

DO - 10.1016/j.cub.2012.11.059

M3 - Article

C2 - 23273897

SN - 0960-9822

VL - 23

SP - 107

EP - 117

JO - Current Biology

JF - Current Biology

IS - 2

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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