Podocalyxin (PODXL) is a transmembrane glycoprotein belonging to the CD34 family of cell surface sialomucins. Initially identified in kidney podocytes, it plays a critical role in maintaining cell polarity, adhesion, and filtration functions. Structurally, PODXL consists of a heavily glycosylated extracellular domain, a single transmembrane region, and a cytoplasmic tail that interacts with cytoskeletal linkers like ezrin and NHERF1. Its expression is not limited to podocytes; it is also found in vascular endothelia, hematopoietic progenitors, and certain epithelial tissues.
In cancer biology, PODXL has emerged as a biomarker of interest due to its overexpression in aggressive malignancies, including carcinomas of the kidney, breast, pancreas, and colorectum. Elevated PODXL levels correlate with enhanced tumor cell invasiveness, metastasis, and poor clinical outcomes, likely mediated through its role in disrupting cell-cell adhesion, promoting epithelial-mesenchymal transition (EMT), and modulating signaling pathways like PI3K/Akt.
PODXL-specific antibodies are widely used in research and diagnostics to assess expression patterns in tissues or cell lines. These antibodies aid in studying its functional roles in development and disease, validating its prognostic significance, and exploring its potential as a therapeutic target. Recent efforts focus on developing anti-PODXL therapies, such as antibody-drug conjugates or immunotherapies, to exploit its tumor-specific expression. However, its dual roles in normal physiology and pathology necessitate careful evaluation of targeting strategies to minimize off-target effects.