PAI-1, encoded by SERPINE1, is a primary member of the serpin super-family and functions as an essential inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen PAI-1 is up-regulated in various pathological states such as vascular diseases, obesity, metabolic syndrome and particularly various types of cancer. PAI-1 expression is quite different in diverse cancer cell lines. PAI-1 is also correlated with poor outcome in several other cancer subtypes, particularly in node-negative breast cancer, ovarian serous carcinoma. As an important regulator of the fibrinolytic system, PAI-1 plays a pivotal role in acute thrombotic events. PAI-1 facilitated invasion and lung metastasis via promoting MMP-13 expression and secretion in osteosarcoma cells, and PAI-1 as well as MMP-13 concomitant expression was significantly associated with lung metastasis of osteosarcoma through clinical samples analysis. 
High PAI-1 expression might increase the risk of head and neck carcinoma metastasis via immunohistochemical analysis and further overexpression of PAI-1 accelerated head and neck cancer cell migration mediated by the activation of PI3K/AKT pathway.  PAI-1 has also been found to promote cell proliferation in fibromatosis and pheochromocytoma. The roles of PAI-1 in cancer might vary with each experimental condition, especially the cancer type. Moreover, PAI-1 may also be involved in immunosuppression, a key condition for rapid tumor progression. Recently, it was reported that TGF-β could enhance PAI-1 secretion in NSCLC dependent on Smad3 phosphorylation, and PAI-1 in return could strengthen TGF-β signaling in tumor associated macrophages via the activation of NF-κB/IL-6/STAT3 pathway, forming an immunosuppressive feed-forward loop.


1.Li S,et al. Biomed Pharmacother. 2018;105:83–94.