Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis.

[en] Plasminogen activator inhibitor-1 (PAI-1) paradoxically enhances tumor progression and angiogenesis; however, the mechanism supporting this role is not known. Here we provide evidence that PAI-1 is essential to protect endothelial cells (ECs) from FasL-mediated apoptosis. In the absence of host-derived PAI-1, human neuroblastoma cells implanted in PAI-1-deficient mice form smaller and poorly vascularized tumors containing an increased number of apoptotic ECs. We observed that knockdown of PAI-1 in ECs enhances cell-associated plasmin activity and increases spontaneous apoptosis in vitro. We further demonstrate that plasmin cleaves FasL at Arg144-Lys145, releasing a soluble proapoptotic FasL fragment from the surface of ECs. The data provide a mechanism explaining the proangiogenic activity of PAI-1.

Research center :

Giga-Cancer - ULiège

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Bajou, Khalid ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire

Peng, H.

Laug, W. E.

Maillard, Catherine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme

Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement

Martial, Joseph ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire

Declerck, Y. A.

Language :

English

Title :

Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis.

Publication date :

2008

Journal title :

Cancer Cell

ISSN :

1535-6108

eISSN :

1878-3686

Publisher :

Elsevier Science

Volume :

Issue :

Pages :

324-34

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 25 March 2009

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Scopus citations^®

127

Scopus citations^®
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121

OpenCitations

103

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