PLAUR

The urokinase plasminogen activator receptor (uPAR, encoded by PLAUR), also known as CD87, is a glycosylphosphatidylinositol (GPI)-anchored cell surface receptor that binds urokinase-type plasminogen activator (uPA) to regulate extracellular matrix degradation and tissue remodeling. By anchoring uPA, uPAR upregulates localized proteolytic activity through plasmin generation, facilitating cell migration, invasion, and intracellular signaling via interactions with integrins and growth factor receptors. Key pathways involving uPAR include the plasminogen activation cascade, MAPK/ERK, and PI3K/AKT signaling. Overexpression of uPAR is clinically linked to tumor metastasis, chronic inflammation, and fibrosis, with elevated levels observed in breast, lung, and colorectal cancers, as well as in atherosclerosis and kidney disease. Therapeutic strategies targeting uPAR include monoclonal antibodies (e.g., ATN-658), small-molecule inhibitors disrupting uPA-uPAR binding, and uPAR-directed CAR-T cells, several of which have shown antitumor efficacy in preclinical models. A phase I trial of the antibody-drug conjugate IMGN901 (anti-uPAR) demonstrated preliminary safety in solid tumors, highlighting its translational potential.