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PAI-1 (plasminogen activator inhibitor-1; SERPINE1) is a
secreted serine-protease inhibitor that primarily inhibits tissue-type and
urokinase-type plasminogen activators (tPA/PLAT and
uPA/PLAU), thereby regulating plasmin generation,
fibrinolysis and extracellular-matrix remodeling. In many cancers, PAI-1 is
overexpressed by tumour cells and stromal cells and can promote tumour-cell
survival, migration, invasion, angiogenesis, epithelial–mesenchymal transition,
metastasis and resistance to therapy through both protease-dependent and
signalling functions involving interactions with vitronectin, integrins and
LRP1. High tumour or circulating PAI-1 is associated with poor prognosis in
several malignancies, particularly breast cancer. The typical cancer-associated
direction is therefore generally up, while the desired
anticancer modulation is commonly down or functional
inhibition. PAI-1 is also strongly associated with cellular senescence and is
frequently used as a component of the senescence-associated secretory phenotype
(SASP), although elevated PAI-1 alone is not sufficient to establish cellular
senescence. PAI-1 is kept separate from PAI-2/SERPINB2 and from its
upstream plasminogen activators uPA and tPA.
In cancer, PAI-1 is commonly upregulated and is associated with invasion, angiogenesis, metastasis, treatment resistance, and poor prognosis, although its biology is context-dependent.
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