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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.

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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.