Good or bad: Paradox of plasminogen activator inhibitor 1 (PAI-1) in digestive system tumors

The fibrinolytic system is involved in many physiological functions, among which the important members can interact with each other, either synergistically or antagonistically to participate in the pathogenesis of many diseases. Plasminogen activator inhibitor 1 (PAI-1) acts as a crucial element of the fibrinolytic system and functions in an anti-fibrinolytic manner in the normal coagulation process. It inhibits plasminogen activator, and affects the relationship between cells and extracellular matrix. PAI-1 not only involved in blood diseases, inflammation, obesity and metabolic syndrome but also in tumor pathology. Especially PAI-1 plays a different role in different digestive tumors as an oncogene or cancer suppressor, even a dual role for the same cancer. We term this phenomenon “PAI-1 paradox”. PAI-1 is acknowledged to have both uPA-dependent and -independent effects, and its different actions can result in both beneficial and adverse consequences. Therefore, this review will elaborate on PAI-1 structure, the dual value of PAI-1 in different digestive system tumors, gene polymorphisms, the uPA-dependent and -independent mechanisms of regulatory networks, and the drugs targeted by PAI-1 to deepen the comprehensive understanding of PAI-1 in digestive system tumors. • PAI-1 is abnormally expressed in various digestive system tumors and closely related to poor prognosis. • The polymorphism of PAI-1 gene predicts the prognosis of digestive tumors. • PAI-1 has uPA-dependent/independent effects and can have both beneficial/adverse consequences with different actions. • Some inhibitors targeting PAI-1 have obtained preliminary efficacy in cancer studies. • Targeting PAI-1 in combination with immunotherapy is an important direction for future research.