Podocalyxin in Normal Tissue and Epithelial Cancer

SIMPLE SUMMARY: Malignancies derived from epithelial cells account for over 90% of all human cancers. Several aspects of cancer progression such as metastasis, immune evasion, and resistance to chemotherapy are often associated with poor prognosis and unfavourable patient outcomes due to limited therapeutic options. Therefore, the discovery of new biomarkers and treatment targets is essential in improving patient prognosis. Podocalyxin, a membrane protein of the CD34 family, has recently gained recognition as a potential diagnostic and prognostic biomarker, as well as a potential target for chemoresistance. This review summarises the current knowledge of podocalyxin in normal tissues and epithelial cancers, highlighting its potential utility in cancer management. ABSTRACT: Podocalyxin (PODXL), a glycosylated cell surface sialomucin of the CD34 family, is normally expressed in kidney podocytes, vascular endothelial cells, hematopoietic progenitors, mesothelium, as well as a subset of neurons. In the kidney, PODXL functions primarily as an antiadhesive molecule in podocyte epithelial cells, regulating adhesion and cell morphology, and playing an essential role in the development and function of the organ. Outside the kidney, PODXL plays subtle roles in tissue remodelling and development. Furthermore, many cancers, especially those that originated from the epithelium, have been reported to overexpress PODXL. Collective evidence suggests that PODXL overexpression is linked to poor prognosis, more aggressive tumour progression, unfavourable treatment outcomes, and possibly chemoresistance. This review summarises our current knowledge of PODXL in normal tissue function and epithelial cancer, with a particular focus on its underlying roles in cancer metastasis, likely involvement in chemoresistance, and potential use as a diagnostic and prognostic biomarker.