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Aberrant glycosylation is a universal feature of cancer cells and plays a key role in tumour growth, immune evasion and metastasis. Alterations in tumour glycosylation are closely associated with prostate cancer progression, making glycans promising therapeutic targets. Fucosyltransferase 8 (FUT8) drives core fucosylation by adding \u03b11,6\u2010fucose to the innermost GlcNAc residue on <jats:italic>N<\/jats:italic>\u2010glycans. While FUT8 is recognised as a crucial factor in cancer progression, its role in prostate cancer remains poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods &amp; Results<\/jats:title><jats:p>Here, we demonstrate using multiple independent clinical cohorts that FUT8 is upregulated in high grade and metastatic prostate tumours, and in the blood of prostate cancer patients with aggressive disease. Using novel tools, including PhosL lectin immunofluorescence and <jats:italic>N<\/jats:italic>\u2010glycan MALDI mass spectrometry imaging (MALDI\u2010MSI), we find FUT8 underpins the biosynthesis of malignant core fucosylated <jats:italic>N<\/jats:italic>\u2010glycans in prostate cancer cells and using both in\u00a0vitro and in\u00a0vivo models, we find FUT8 promotes prostate tumour growth, cell motility and invasion. Mechanistically we show FUT8 regulates the expression of genes and signalling pathways linked to prostate cancer progression. Furthermore, we find that fucosylation inhibitors can inhibit the activity of FUT8 in prostate cancer to suppress the growth of prostate tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study cements FUT8\u2010mediated core fucosylation as an important driver of prostate cancer progression and suggests targeting FUT8 activity for prostate cancer therapy as an exciting area to explore.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70959","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T13:11:40Z","timestamp":1747660300000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>FUT8<\/scp> Is a Critical Driver of Prostate Tumour Growth and Can Be Targeted Using Fucosylation Inhibitors"],"prefix":"10.1002","volume":"14","author":[{"given":"Kayla","family":"Bastian","sequence":"first","affiliation":[{"name":"Newcastle University Centre for Cancer Newcastle University Institute of Biosciences  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Orozco\u2010Moreno","sequence":"additional","affiliation":[{"name":"Newcastle University Centre for Cancer Newcastle University Institute of Biosciences  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw","family":"Thomas","sequence":"additional","affiliation":[{"name":"Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Paul O'gorman Building Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Newcastle University Centre for Cancer Newcastle University Institute of Biosciences  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline A.","family":"Visser","sequence":"additional","affiliation":[{"name":"Synthetic Organic Chemistry, Institute for Molecules and Materials Radboud University  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiel","family":"Rossing","sequence":"additional","affiliation":[{"name":"Synthetic Organic Chemistry, Institute for Molecules and Materials Radboud University  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan F. 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