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

被引:0
作者
Marta Helena Kubala
Yves Albert DeClerck
机构
[1] University of Southern California,Division of Hematology, Oncology and Blood and Bone Marrow Transplantation, Department of Pediatrics
[2] The Saban Research Institute of Children’s Hospital,Department of Biochemistry and Molecular Medicine
[3] University of Southern California,undefined
来源
Cancer and Metastasis Reviews | 2019年 / 38卷
关键词
Plasminogen activator inhibitor 1; PAI-1; Protease inhibitor; SerpinE1; Tumor microenvironment; Inflammation;
D O I
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中图分类号
学科分类号
摘要
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.
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页码:483 / 492
页数:9
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