uPa

Urokinase-type plasminogen activator (uPA) is a secreted serine protease that belongs to the plasminogen activator family. Its primary biochemical role is to convert plasminogen into plasmin, an enzyme that degrades fibrin and other components of the extracellular matrix. Through this proteolytic activity, uPA initiates pericellular proteolysis that contributes to tissue remodeling, cell migration, and invasion.

uPA is synthesized as a single-chain zymogen (single-chain uPA) and is activated by proteolytic cleavage to an active, two-chain form. The activity and localization of uPA are tightly regulated by its binding to the cell surface receptor uPAR (CD87). The uPA-uPAR complex concentrates plasminogen activation at the cell surface, focusing proteolysis to the pericellular environment and facilitating interactions with other proteolytic systems such as matrix metalloproteinases.

Physiologically, uPA participates in processes such as wound healing, embryonic development, and tissue remodeling. It also plays a role in normal fibrinolysis by generating plasmin to dissolve clots. Dysregulation of the uPA–plasminogen system can contribute to pathological tissue invasion and metastasis in cancer, where high uPA activity and/or elevated uPAR expression have been associated with poor prognosis in several tumor types.

Clinically, urinary-type uPA and its receptor, along with plasminogen activator inhibitor-1 (PAI-1), are studied as prognostic biomarkers in cancers, particularly breast cancer, to help assess risk and guide treatment decisions. Therapeutic approaches targeting the uPA–uPAR axis are under investigation but are not established standard care.