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ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis.

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Mavria G,Vercoulen Y,Yeo M,Paterson H,Karasarides M,Marais R,Bird D,Marshall CJ

doi

10.1016/j.ccr.2005.12.021

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

33-44

issue

1

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(05)00397-1

journal_volume

9

pub_type

杂志文章

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