ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis.
Cancer Cell
; 9(1): 33-44, 2006 Jan.
Article
em En
| MEDLINE
| ID: mdl-16413470
ABSTRACT
Inhibition of ERK-MAPK signaling by expression of dominant-negative MEK1 in the tumor vasculature suppresses angiogenesis and tumor growth. In an organotypic tissue culture angiogenesis assay, ERK-MAPK inhibition during the migratory phase results in loss of bipolarity, detachment, and cell death of isolated endothelial cells and retraction of sprouting tubules. These effects are the consequence of upregulated Rho-kinase signaling. Transient inhibition of Rho-kinase rescues the effects of ERK-MAPK inhibition in vitro and in vivo, promotes sprouting, and increases vessel length in tumors. We propose a regulatory role of Rho-kinase by ERK-MAPK during angiogenesis that acts through the control of actomyosin contractility. Our data delineate a mechanism by which ERK-MAPK promotes endothelial cell survival and sprouting by downregulating Rho-kinase signaling.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Proteínas Serina-Treonina Quinases
/
Proteínas Quinases Ativadas por Mitógeno
/
Células Endoteliais
/
MAP Quinase Quinase 1
/
Neovascularização Patológica
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article