Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-kappaB activation and endothelial cell survival.
Détails
ID Serval
serval:BIB_E8627C181722
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-kappaB activation and endothelial cell survival.
Périodique
Oncogene
ISSN
0950-9232
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
26
Numéro
39
Pages
5722-32
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
Tumor necrosis factor (TNF) is a pro-inflammatory cytokine exerting pleiotropic effects on endothelial cells. Depending on the vascular context it can induce endothelial cell activation and survival or death. The microenvironmental cues determining whether endothelial cells will survive or die, however, have remained elusive. Here we report that integrin ligation acts permissive for TNF-induced protein kinase B (PKB/Akt) but not nuclear factor (NF)-kappaB activation. Concomitant activation of PKB/Akt and NF-kappaB is essential for the survival of endothelial cells exposed to TNF. Active PKB/Akt strengthens integrin-dependent endothelial cell adhesion, whereas disruption of actin stress fibers abolishes the protective effect of PKB/Akt. Integrin-mediated adhesion also represses TNF-induced JNK activation, but JNK activity is not required for cell death. The alphaVbeta3/alphaVbeta5 integrin inhibitor EMD121974 sensitizes endothelial cells to TNF-dependent cytotoxicity and active PKB/Akt attenuates this effect. Interferon gamma synergistically enhanced TNF-induced endothelial cell death in all conditions tested. Taken together, these observations reveal a novel permissive role for integrins in TNF-induced PKB/Akt activation and prevention of TNF-induced death distinct of NF-kappaB, and implicate the actin cytoskeleton in PKB/Akt-mediated cell survival. The sensitizing effect of EMD121974 on TNF cytotoxicity may open new perspectives to the therapeutic use of TNF as anticancer agent.
Mots-clé
Actins, Apoptosis, Blotting, Western, Cell Adhesion, Cells, Cultured, Cytoskeleton, Electrophoretic Mobility Shift Assay, Endothelium, Vascular, Flow Cytometry, Humans, In Situ Nick-End Labeling, Integrin alphaVbeta3, Integrins, MAP Kinase Kinase 4, NF-kappa B, Phosphorylation, Proto-Oncogene Proteins c-akt, Receptors, Vitronectin, Signal Transduction, Spheroids, Cellular, Tumor Necrosis Factor-alpha
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 9:36
Dernière modification de la notice
20/08/2019 17:11