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. Remarkably, high PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumour types, such as prostate cancer. We performed extensive in vitro analysis of prostate cancer cell lines that have the highest RNA levels of PODXL (PC3). We identified that elevated PODXL promoted invasion. We also isolated 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.By using proteomic analysis, we aimed to identify the strongest interactors of PODXL, trying to uncover molecular mechanisms that control PODXL function and localization.