Loss of profilin-1 expression enhances breast cancer cell motility by Ena/VASP proteins.
J Cell Physiol
; 219(2): 354-64, 2009 May.
Article
en En
| MEDLINE
| ID: mdl-19115233
We previously showed that silencing profilin-1 (Pfn1) expression increases breast cancer cell motility, but the underlying mechanisms have not been explored. Herein, we demonstrate that loss of Pfn1 expression leads to slower but more stable lamellipodial protrusion thereby enhancing the net protrusion rate and the overall motility of MDA-MB-231 breast cancer cells. Interestingly, MDA-MB-231 cells showed dramatic enrichment of VASP at their leading edge when Pfn1 expression was downregulated and this observation was also reproducible in other cell types including human mammary epithelial cells and vascular endothelial cells. We further demonstrate that Pfn1 downregulation results in a hyper-motile phenotype of MDA-MB-231 cells in an Ena/VASP-dependent mechanism. Pfn1-depleted cells display a strong colocalization of VASP with lamellipodin (Lpd--a PI(3,4)P(2)-binding protein that has been previously implicated in lamellipodial targeting of Ena/VASP) at the leading edge. Finally, inhibition of PI3-kinase (important for generation of PI(3,4)P(2)) delocalizes VASP from the leading edge. This observation is consistent with a possible involvement of Lpd in enhanced membrane recruitment of VASP that results from loss of Pfn1 expression. Our findings for the first time highlight a possible mechanism of how reduced expression of a pro-migratory molecule like Pfn1 could actually promote motility of breast cancer cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
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Neoplasias de la Mama
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Moléculas de Adhesión Celular
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Movimiento Celular
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Profilinas
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Proteínas de Microfilamentos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Cell Physiol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos