Spatial regulation of the glycocalyx component Podocalyxin is a switch for pro-metastatic function

The sialomucin Podocalyxin (PODXL) is required for normal tissue development and apicobasal cell polarity by promoting lumen formation. Strikingly, high PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumour types, such as prostate cancer. Utilising prostate cancer cell lines that have the highest RNA levels of PODXL (PC3), we identified subpopulations that do not differ drastically in their overall expression of PODXL but have the stable feature of either high or low surface localisation of PODXL. High surface PODXL promote robust invasion of cells into extracellular matrix. Notably, knockdown of PODXL gave the same effect - reduced invasion - as having PODXL expressed but not being localised to the surface. We performed transcriptional profiling via RNA-sequencing of PC3 cells (PC3 parental, PC3 High surface PODXL and PC3 Low surface PODXL) to uncover possible regulators of PODXL surface expression.