[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/Unit :
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.
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