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Lookup NU author(s): Dr Emma ScottORCiD, Dr Kirsty Hodgson, Kat Cheung, Edward Yo, Laura WilsonORCiD, Huw ThomasORCiD, Maggie Orozco Moreno, Kayla Bastian, Lois Kelly, Dr Gerald Hysenaj, Emily Archer Goode, Rebecca Garnham, Adam Duxfield, Professor Rakesh Heer, Professor David Elliott, Dr Jennifer Munkley
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s).Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression.
Author(s): Scott E, Hodgson K, Calle B, Turner H, Cheung K, Bermudez A, Marques FJG, Pye H, Yo EC, Islam K, Oo HZ, McClurg UL, Wilson L, Thomas H, Frame FM, Orozco-Moreno M, Bastian K, Arredondo HM, Roustan C, Gray MA, Kelly L, Tolson A, Mellor E, Hysenaj G, Goode EA, Garnham R, Duxfield A, Heavey S, Stopka-Farooqui U, Haider A, Freeman A, Singh S, Johnston EW, Punwani S, Knight B, McCullagh P, McGrath J, Crundwell M, Harries L, Bogdan D, Westaby D, Fowler G, Flohr P, Yuan W, Sharp A, de Bono J, Maitland NJ, Wisnovsky S, Bertozzi CR, Heer R, Guerrero RH, Daugaard M, Leivo J, Whitaker H, Pitteri S, Wang N, Elliott DJ, Schumann B, Munkley J
Publication type: Article
Publication status: Published
Journal: Oncogene
Year: 2023
Volume: 42
Pages: 926–937
Print publication date: 16/03/2023
Online publication date: 01/02/2023
Acceptance date: 19/01/2023
Date deposited: 13/02/2023
ISSN (print): 0950-9232
ISSN (electronic): 1476-5594
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41388-023-02604-x
DOI: 10.1038/s41388-023-02604-x
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