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A major driver of its aggressiveness is the tumour microenvironment (TME), which fuels tumour growth, metastasis, and therapeutic resistance through dynamic, bi\u2010directional communication between cancer cells, fibroblasts, and immune cells. Emerging evidence highlights extracellular vesicles (EVs) as key mediators of oncogenic cross\u2010talk within the PaC TME. This study demonstrates for the first time that the overexpression of metastasis suppressor N\u2010myc downstream regulated gene 1 (NDRG1) significantly influences the biogenesis, cargo packaging and release of EVs by cancer cells. This was mediated by a direct interaction between NDRG1 and ALIX, a key protein involved in EV biogenesis and packaging, with NDRG1 facilitating ALIX proteasomal degradation. 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These findings uncover a previously unrecognized mechanism by which NDRG1 overexpression disrupts the oncogenic two\u2010way communication between PaC cells and the TME, positioning NDRG1 overexpression as a compelling therapeutic approach against this formidable malignancy.<\/jats:p>","DOI":"10.1002\/jev2.70334","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:18:57Z","timestamp":1782854337000},"source":"Crossref","is-referenced-by-count":0,"title":["Silencing the Signal: The Metastasis Suppressor NDRG1 Disrupts Small Extracellular Vesicle\u2010Mediated Crosstalk in Pancreatic Cancer"],"prefix":"10.1002","volume":"15","author":[{"given":"Jiawei","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Physiology School of Biomedical Sciences Faculty of Medicine and Health University of NSW  Sydney 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