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The role of GCNT1 mediated O-glycosylation in aggressive prostate cancer

Lookup NU author(s): Dr Kirsty Hodgson, Maggie Orozco Moreno, Dr Emma ScottORCiD, Rebecca Garnham, Karen Livermore, Huw ThomasORCiD, Kayla Bastian, Dr Gerald Hysenaj, Emily Archer Goode, 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, Springer Nature Limited.Prostate cancer is the most common cancer in men and a major cause of cancer related deaths worldwide. Nearly all affected men develop resistance to current therapies and there is an urgent need to develop new treatments for advanced disease. Aberrant glycosylation is a common feature of cancer cells implicated in all of the hallmarks of cancer. A major driver of aberrant glycosylation in cancer is the altered expression of glycosylation enzymes. Here, we show that GCNT1, an enzyme that plays an essential role in the formation of core 2 branched O-glycans and is crucial to the final definition of O-glycan structure, is upregulated in aggressive prostate cancer. Using in vitro and in vivo models, we show GCNT1 promotes the growth of prostate tumours and can modify the glycome of prostate cancer cells, including upregulation of core 2 O-glycans and modifying the O-glycosylation of secreted glycoproteins. Furthermore, using RNA sequencing, we find upregulation of GCNT1 in prostate cancer cells can alter oncogenic gene expression pathways important in tumour growth and metastasis. Our study highlights the important role of aberrant O-glycosylation in prostate cancer progression and provides novel insights regarding the mechanisms involved.


Publication metadata

Author(s): Hodgson K, Orozco-Moreno M, Scott E, Garnham R, Livermore K, Thomas H, Zhou Y, He J, Bermudez A, Garcia Marques FJ, Bastian K, Hysenaj G, Archer Goode E, Heer R, Pitteri S, Wang N, Elliott DJ, Munkley J

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2023

Volume: 13

Issue: 1

Online publication date: 09/10/2023

Acceptance date: 18/09/2023

Date deposited: 30/10/2023

ISSN (electronic): 2045-2322

Publisher: Nature Research

URL: https://doi.org/10.1038/s41598-023-43019-8

DOI: 10.1038/s41598-023-43019-8

PubMed id: 37813880


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Funding

Funder referenceFunder name
6961
Mark Foundation for Cancer Research
J.G.W. Patterson Foundation
Prostate Cancer UK
Prostate Cancer UK Travelling Prize Fellowship
RIA16-ST2-011Prostate Cancer UK (Formerly Prostate Cancer Charity)
The Bob Willis Fund
TLD-PF19-002
Prostate Cancer Research

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