| First Author | Bajou K | Year | 2008 |
| Journal | Cancer Cell | Volume | 14 |
| Issue | 4 | Pages | 324-34 |
| PubMed ID | 18835034 | Mgi Jnum | J:140088 |
| Mgi Id | MGI:3811928 | Doi | 10.1016/j.ccr.2008.08.012 |
| Citation | Bajou K, et al. (2008) Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis. Cancer Cell 14(4):324-34 |
| abstractText | 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. |
