WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression

Khalid Sossey-Alaoui, Tamara A. Ranalli, Xiurong Li, Andrei V. Bakin, John Kenneth Cowell

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

WAVE3 is a member of the WASP/WAVE family of proteins, which play a critical role in the regulation of actin polymerization, cytoskeleton organization, and cell motility. We show here that knockdown of the WAVE3 protein, using RNA interference in MDA-MB-231 cells, decreases phospho-p38 MAPK levels, but not those of phospho-AKT, phospho-ERK, or phospho-JNK. Knockdown of WAVE3 expression also inhibited the expression levels of MMP-1, MMP-3, and MMP-9, but not MMP-2. MMP production could be restored by PMA treatment, without affecting siRNA-mediated WAVE3 knockdown. The WAVE3-mediated downregulation of p38 activity and MMP production is independent of the presence of both WAVE1 and WAVE2, whose expression levels were not affected by loss of WAVE3. We also show that the downstream effect of the WAVE3 knockdown is the inhibition of cell motility and invasion, coupled with increased actin stress fiber formation, as well as reorganization of focal adhesion complexes. These findings suggest that WAVE3 regulates actin cytoskeleton, cell motility, and invasion through the p38 MAPK pathway and MMP production.

Original languageEnglish (US)
Pages (from-to)135-145
Number of pages11
JournalExperimental Cell Research
Volume308
Issue number1
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

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Matrix Metalloproteinases
Cell Movement
Wiskott-Aldrich Syndrome Protein Family
p38 Mitogen-Activated Protein Kinases
Actin Cytoskeleton
Stress Fibers
Focal Adhesions
RNA Interference
Polymerization
Small Interfering RNA
Actins
Down-Regulation

Keywords

  • Cell motility
  • MMP
  • WAVE3

ASJC Scopus subject areas

  • Cell Biology

Cite this

WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression. / Sossey-Alaoui, Khalid; Ranalli, Tamara A.; Li, Xiurong; Bakin, Andrei V.; Cowell, John Kenneth.

In: Experimental Cell Research, Vol. 308, No. 1, 01.08.2005, p. 135-145.

Research output: Contribution to journalArticle

Sossey-Alaoui, Khalid ; Ranalli, Tamara A. ; Li, Xiurong ; Bakin, Andrei V. ; Cowell, John Kenneth. / WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression. In: Experimental Cell Research. 2005 ; Vol. 308, No. 1. pp. 135-145.
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