The plasminogen activator inhibitor-1 paradox in cancer: a mechanistic understanding

• Published in: Cancer and metastasis reviews 2019-09, Vol.38 (3), p.483-492
• Main Authors: Kubala, Marta Helena, DeClerck, Yves Albert
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Antifibrinolytic agents; Apoptosis; Biomarkers, Tumor - chemistry; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cell survival; Development and progression; Disease Progression; Fibrin; Health aspects; Humans; Metastases; Metastasis; Models, Molecular; Neoplasms - blood supply; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Oncology; Plasminogen Activator Inhibitor 1 - chemistry; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Plasminogen activator inhibitors; Polymorphism, Single Nucleotide; Randomized Controlled Trials as Topic; Thrombolytic drugs; U-Plasminogen activator
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-019-09806-4

The paradoxical pro-tumorigenic function of plasminogen activator inhibitor 1 (PAI-1, aka Serpin E1) in cancer progression and metastasis has been the subject of an abundant scientific literature that has pointed to a pro-angiogenic role, a growth and migration stimulatory function, and an anti-apoptotic activity, all directed toward promoting tumor growth, cancer cell survival, and metastasis. With uPA, PAI-1 is among the most reliable biomarkers and prognosticators in many cancer types. More recently, a novel pro-tumorigenic function of PAI-1 in cancer-related inflammation has been demonstrated. These multifaceted activities of PAI-1 in cancer progression are explained by the complex structure of PAI-1 and its multiple functions that go beyond its anti-fibrinolytic and anti-plasminogen activation activities. However, despite the multiple evidences supporting a pro-tumorigenic role of PAI-1 in cancer, and the development of several inhibitors, targeting PAI-1, has remained elusive. In this article, the various mechanisms responsible for the pro-tumorigenic functions of PAI-1 are reviewed with emphasis on its more recently described contribution to cancer inflammation. The challenges of targeting PAI-1 in cancer therapy are then discussed.