Description
Plasminogen activator inhibitor 1 (PAI-1) is a peptide protease inhibitor that exhibits proliferation-enhancing activity in cancer models. PAI-1 is produced by thrombin activation of protease-activated receptor 1 (PAR1) and is clinically used as a biomarker for heart disease. PAI-1 increases cell proliferation and tumor size of HeLa xenografts in some models and may be over-expressed in cancerous tissue. In other animal models of cancer, PAI-1 exhibits anti-apoptotic activity through a mechanism that involved activation of plasmin and inhibition of Fas/FasL signaling. PAI-1 also displays pro-fibrotic characteristics and plays a role in type 1 diabetic osteoporosis; it promotes proliferation of pulmonary fibroblasts, enhances their transition to myofibroblasts, and increases collagen synthesis and activation of ERK and Akt.
References
Gomes Giacoia E, Miyake M, Lawton A, et al. PAI-1 Leads to G1-phase Cell Cycle Progression through Cyclin D3/CDK4/6 Up-regulation. Mol Cancer Res. 2014 Jan 24. [Epub ahead of print]. PMID: 24464915.
Tamura Y, Kawao N, Okada K, et al. Plasminogen activator inhibitor-1 is involved in streptozotocin-induced bone loss in female mice. Diabetes. 2013 Sep;62(9):3170-9. PMID: 23715621.
Zhang YP, Wang WL, Liu J, et al. Plasminogen activator inhibitor-1 promotes the proliferation and inhibits the apoptosis of pulmonary fibroblasts by Ca(2+) signaling. Thromb Res. 2013 Jan;131(1):64-71. PMID: 23021499.
Fang H, Placencio VR, DeClerck YA. Protumorigenic activity of plasminogen activator inhibitor-1 through an antiapoptotic function. J Natl Cancer Inst. 2012 Oct 3;104(19):1470-84. PMID: 22984202.
McEachron TA, Church FC, Mackman N. Regulation of thrombin-induced plasminogen activator inhibitor-1 in 4T1 murine breast cancer cells. Blood Coagul Fibrinolysis. 2011 Oct;22(7):576-82. PMID: 21799402.
