Regulation of programmed cell death by plasminogen activator inhibitor type 1 (PAI-1).
Elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with poor prognosis in cancer. An explanation to the elevated levels of PAI-1 could be a protective response to the increased proteolytic activity, caused by elevated levels of urokinase-type plasminogen activator (uPA) observed in tumours; however, several lines of evidence suggest that PAI-1 may contribute directly to the pathology of the disease. PAI-1 has been reported to have an effect on most of the basic cellular processes including cell adhesion, cell migration, cell invasion, and cell proliferation and increasing numbers of reports suggest that PAI-1 also can regulate programmed cell death (PCD) in cancer cells and normal cells. A number of reports suggest that PAI-1 can inhibit PCD through its pro-adhesive/anti-proteolytic property whereas other reports suggest that PAI-1 induces PCD through its anti-adhesive property. Furthermore, it has been suggested that PAI-1 can either induce or inhibit PCD though activation of cell signalling pathways. This review will focus on the regulation of programmed cell death by PAI-1 in both normal cells and cancer cells.
Lademann
Ulrik A
UA
Department of Disease Biology, Section for Biomedicine, Faculty of Life Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg C., Denmark. ul@life.ku.dk
Rømer
Maria Unni
MU
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1