Down-regulation of WAVE3, a metastasis promoter gene, inhibits invasion and metastasis of breast cancer cells

Khalid Sossey-Alaoui, Alfiya Safina, Xiurong Li, Mary M. Vaughan, David G. Hicks, Andrei V. Bakin, John Kenneth Cowell

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The expression of WAVE3, an actin-cytoskeleton and reorganization protein, is elevated in malignant human breast cancer, yet the role of WAVE3 in promoting tumor progression remains undefined. We have recently shown that knockdown of WAVE3 expression in human breast adenocarcinoma MDA-MB-231 cells using small interfering RNA resulted in a significant reduction of cell motility, migration, and invasion, which correlated with a reduction in the levels of active p38 mitogen-activated protein kinase. Here, we investigated the effect of stable suppression of WAVE3 by short hairpin RNA on tumor growth and metastasis in xenograft models. Breast cancer MDA-MB-231 cells expressing short hairpin RNA to WAVE3 (shWAVE3) showed a significant reduction in Matrigel invasion and formation of lung colonies after tail-vein injection in SCID mice. In the orthotopic model, we observed a reduction in growth rate of the primary tumors, as well as in the metastases to the lungs. We also show that suppression of p38 mitogen-activated protein kinase activity by dominant-negative p38 results in comparable phenotypes to the knockdown of WAVE3. These studies provide direct evidence that the WAVE3-p38 pathway contributes to breast cancer progression and metastasis.

Original languageEnglish (US)
Pages (from-to)2112-2121
Number of pages10
JournalAmerican Journal of Pathology
Volume170
Issue number6
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

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Small Interfering RNA
Down-Regulation
p38 Mitogen-Activated Protein Kinases
Breast Neoplasms
Neoplasm Metastasis
Cell Movement
Genes
Neoplasms
Lung
SCID Mice
Growth
Actin Cytoskeleton
Heterografts
Tail
Veins
Adenocarcinoma
Breast
Phenotype
Injections
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Down-regulation of WAVE3, a metastasis promoter gene, inhibits invasion and metastasis of breast cancer cells. / Sossey-Alaoui, Khalid; Safina, Alfiya; Li, Xiurong; Vaughan, Mary M.; Hicks, David G.; Bakin, Andrei V.; Cowell, John Kenneth.

In: American Journal of Pathology, Vol. 170, No. 6, 01.01.2007, p. 2112-2121.

Research output: Contribution to journalArticle

Sossey-Alaoui, Khalid ; Safina, Alfiya ; Li, Xiurong ; Vaughan, Mary M. ; Hicks, David G. ; Bakin, Andrei V. ; Cowell, John Kenneth. / Down-regulation of WAVE3, a metastasis promoter gene, inhibits invasion and metastasis of breast cancer cells. In: American Journal of Pathology. 2007 ; Vol. 170, No. 6. pp. 2112-2121.
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