biostudies-literatureRoman-Fernandez ACancer Research UKMedical Research CouncilNCI NIH HHSeabq1858https://www.ebi.ac.uk/biostudies/studies/S-EPMC9897673biostudies-literatureUnknown9(5)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 of integrin-based invasion. Differential cortical targeting of PODXL, regulated by ubiquitination, is the molecular mechanism controlling alternate fates. Both PODXL high and low surface levels occur in parallel subpopulations within cancer cells. Orthotopic intraprostatic xenograft of PODXL-manipuScience advancesSpatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function.PMC9897673MR/P01058X/1298012980029799K99 CA16353528291MR/T040769/1Roman-Fernandez AKatoch ACumming EMStrachan DLeung HYShaw RPatel RGalbraith LNikolatou KNixon CMiller CJMason SMansour MAAnand JSandilands EPark JBlyth KKugeratski FGBryant DMFreckmann ECCampbell KJMcGarry LZanivan SRakovic KLe Quesne JNorman JCLilla SfalseSpatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function.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 of integrin-based invasion. Differential cortical targeting of PODXL, regulated by ubiquitination, is the molecular mechanism controlling alternate fates. Both PODXL high and low surface levels occur in parallel subpopulations within cancer cells. Orthotopic intraprostatic xenograft of PODXL-manipu2023-01-01T00:00:00Z2023 Feb2026-05-28T11:52:21.024Z2025-04-07T03:18:39.47ZS-EPMC98976733673578210.1126/sciadv.abq1858