Abstract
Simple SummaryMalignancies 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.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.
Highlights
The epithelium consists of a layer of apical-basally polarised cells that line the cavity and surfaces of organs throughout the body
While PODXL is detected in normal tissues of the kidney, breast, liver, pancreas, and endometrium [11,12], overexpression of PODXL has been associated with poor prognosis and outcomes of several epithelial cancers, including breast and ovarian carcinomas [13,14]
Ezrin was not identified in immunoprecipitated PODXL from SW1990 pancreatic cells, and PODXL knockdown failed to alter the activities of RhoA and Rac1, which are often induced by PODXL–ezrin binding; these results suggest that PODXL does not associate with ezrin in pancreatic cancer cells [18]
Summary
The epithelium consists of a layer of apical-basally polarised cells that line the cavity and surfaces of organs throughout the body. Depending on their location, epithelial cells may serve several functions including barrier protection, secretion, and absorption [1]. While PODXL is detected in normal tissues of the kidney, breast, liver, pancreas, and endometrium [11,12], overexpression of PODXL has been associated with poor prognosis and outcomes of several epithelial cancers, including breast and ovarian carcinomas [13,14]. PODXL may be a potential biomarker for predicting patient outcomes and identifying subgroups with higher risks of developing aggressive cancer phenotypes [15,19]. We examine the mechanisms of PODXL in cancer progression and its potential as a biomarker in the diagnosis, prognosis, and treatment of epithelial cancers
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