PAI-1: A Multifunctional SERPIN with Complex Roles in Cell Signaling and Migration

Elevated levels of plasminogen activator inhibitor type-1 (PAI-1) often occur in concert with the conversion of non-motile epithelial elements into a more migratory phenotype. While essential during embryonic development, this restructuring process, referred to as epithelial-to-mesenchymal-transition (EMT) is limited in the adult organism, occurring normally during wound repair or more atypically in tumor progression. Cell motility, the focal point of EMT, requires the coordinate regulation of multiple mechanisms which ensure proper communication between cell surface receptors and the extracellular environment. PAI-1, through multifaceted interactions with both extracellular matrix (ECM) and cell surface constituents plays a critical role in modulating many of these events. This review focuses on the complex role of PAI-1 in the cellular motile program.