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Current screening methods lack precision in distinguishing aggressive cases, emphasizing a need for tissue\u2010based biomarkers. Although Golgi disorganization, ER stress, and elevated high\u2010mannose (Man) glycoproteins (e.g., Integrin \u03b1\n                    <jats:sub>v<\/jats:sub>\n                    , key metastatic player) are recognized features of metastatic prostate tumors, their interrelationships remain unexplored. It is observed that the growth of primary prostate tumors is linked to an increase in endoplasmic reticulum (ER)\u2013plasma membrane (PM) junctions signaling, mediated by STIM1 and ORP5. However, transition to lymph node and tissue metastasis is associated with their downregulation, loss of ER\u2013PM communications, significant Golgi dispersal, and rapid conversion of high\u2010Man glycans in the Golgi to atypical MGAT5\u2010modified sugars that facilitate Integrin \u03b1\n                    <jats:sub>v<\/jats:sub>\n                    clustering at the PM via Galectin\u20103 binding. Golgi dispersal is associated with increased organelle volume and surface area to accommodate heightened trafficking and processing. These findings position STIM1 and ORP5 as biomarkers of aggressive PCa and show that high\u2010Man enrichment is not due to defective maturation but reflects a glycan pool that cancer cells actively utilize, suggesting that the concept of ER stress response in PCa should be redefined to include Golgi reorganization and altered ER\u2013PM junctions.\n                  <\/jats:p>","DOI":"10.1002\/advs.202522885","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:49:28Z","timestamp":1770900568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dynamic Shifts in ER\u2013Plasma Membrane Junctions Signaling Define Pro\u2010Metastatic N\u2010Glycosylation and Predict Prostate Cancer Progression"],"prefix":"10.1002","volume":"13","author":[{"given":"Amanda J.","family":"Macke","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology University of 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