Proteomics

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


ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Prostate Cancer

SUBMITTER: Sergio Lilla  

LAB HEAD: Sara Rossana Zanivan

PROVIDER: PXD032911 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications


The glycocalyx component and sialomucin podocalyxin (PODXL) is required for normal tissue development by promoting apical membranes to form between cells, triggering lumen formation. Elevated PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumor types. How PODXL presents this duality in effect remains unknown. We identify an unexpected function of PODXL as a decoy receptor for galectin-3 (GAL3), whereby the PODXL-GAL3 interaction releases GAL3 repression  ...[more]

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