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Lookup NU author(s): Kayla Bastian, Maggie Orozco MorenoORCiD, Huw ThomasORCiD, Dr Kirsty HodgsonORCiD, Laura WilsonORCiD, Oliver Hanley, Jess Peng, Professor Rakesh Heer, Dr Emma ScottORCiD, Professor David ElliottORCiD, Dr Jennifer MunkleyORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.Background: An unmet clinical need requires the discovery of new treatments for men facing advanced prostate cancer. 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 α1,6-fucose to the innermost GlcNAc residue on N-glycans. While FUT8 is recognised as a crucial factor in cancer progression, its role in prostate cancer remains poorly understood. Methods & Results: 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 N-glycan MALDI mass spectrometry imaging (MALDI-MSI), we find FUT8 underpins the biosynthesis of malignant core fucosylated N-glycans in prostate cancer cells and using both in vitro and in vivo 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. Conclusions: Our study cements FUT8-mediated 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.
Author(s): Bastian K, Orozco-Moreno M, Thomas H, Hodgson K, Visser EA, Rossing E, Pijnenborg JFA, Eerden N, Wilson L, Saravannan H, Hanley O, Grimsley G, Frame F, Peng Z, Knight B, McCullagh P, McGrath J, Crundwell M, Harries L, Maitland NJ, Heer R, Wang N, Goddard-Borger ED, Guerrero RH, Boltje TJ, Drake RR, Scott E, Elliott DJ, Munkley J
Publication type: Article
Publication status: Published
Journal: Cancer Medicine
Year: 2025
Volume: 14
Issue: 10
Online publication date: 19/05/2025
Acceptance date: 29/04/2025
Date deposited: 03/06/2025
ISSN (print): 2045-7634
ISSN (electronic): 2045-7634
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/cam4.70959
DOI: 10.1002/cam4.70959
Data Access Statement: The data that supports the findings of this study are available in the Supporting Information of this article.
PubMed id: 40387385
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