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Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth

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

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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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Funding

Funder referenceFunder name
6961
FC001749
R01 CA200423
RIA16-ST2-011Prostate Cancer UK (Formerly Prostate Cancer Charity)
TLD-PF19-002
U01 CA196387
RR005351
W81XWH-18-2-0013
W81XWH-18-2-0017
TFRI-NF-PPG
W81XWH-18-2-0015
W81XWH-18-2-0016
W81XWH-18-2-0018
W81XWH-18-2-0019

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