Open AccessThe plasminogen activator inhibitor-1 paradox in cancer: a mechanistic understanding
Author(s) -
Marta H. Kubala,
Yves A. DeClerck
Publication year - 2019
Publication title -
cancer and metastasis reviews/cancer metastasis reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.555
H-Index - 148
eISSN - 1573-7233
pISSN - 0167-7659
DOI - 10.1007/s10555-019-09806-4
Subject(s) - serpin , metastasis , cancer , cancer research , plasminogen activator , plasminogen activator inhibitor 1 , tumor progression , inflammation , cancer cell , carcinogenesis , biology , function (biology) , immunology , medicine , microbiology and biotechnology , endocrinology , biochemistry , gene
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.