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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
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 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.
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
Data Access Statement: The data that support the findings of this study are openly available and can be accessed on GEO repository (GSE224036).
PubMed id: 37813880
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