PDPN

Podoplanin (PDPN), also known as Aggrus or T1-alpha, is a transmembrane glycoprotein critically involved in cell migration, platelet aggregation, and lymphatic vascular development. It mediates cellular effects by binding to C-type lectin-like receptor 2 (CLEC-2) on platelets, triggering downstream signaling through Syk/SLP-76 and PI3K/AKT pathways, which regulate cytoskeletal reorganization and metastatic dissemination. PDPN is overexpressed in multiple cancers, including glioblastoma, squamous cell carcinoma, and melanoma, where it promotes tumor invasiveness, epithelial-mesenchymal transition, and lymphatic metastasis via interactions with ERM proteins (ezrin/radixin/moesin). Clinically, PDPN correlates with poor prognosis in lung adenocarcinoma and Kaposi sarcoma. It also contributes to inflammatory diseases like rheumatoid arthritis by activating fibroblast-like synoviocytes. Current therapeutic strategies focus on monoclonal antibodies (e.g., NZ-1) and CAR-T cells targeting PDPN in clinical trials for brain tumors. Small-molecule inhibitors disrupting PDPN-CLEC-2 interactions are under preclinical evaluation for antimetastatic applications.