TY - JOUR
T1 - WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression
AU - Sossey-Alaoui, Khalid
AU - Ranalli, Tamara A.
AU - Li, Xiurong
AU - Bakin, Andrei V.
AU - Cowell, John K.
N1 - Funding Information:
We thank Erica VanDette for vinculin immunostaining and Lisa Wylie for editorial assistance. This research was supported in part by a grant from the Association for Research on Children Cancer #62-3027-01 to KSA, by an Institutional Research Grant #IRG02-197-01 from the American Cancer Society to KSA, by NIH grant # NS35791-05 to JKC, and by the NCI-funded Cancer Center Support Grant CA16056.
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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.
AB - 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.
KW - Cell motility
KW - MMP
KW - WAVE3
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U2 - 10.1016/j.yexcr.2005.04.011
DO - 10.1016/j.yexcr.2005.04.011
M3 - Article
C2 - 15907837
AN - SCOPUS:22144437275
SN - 0014-4827
VL - 308
SP - 135
EP - 145
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -