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

Authors :
Hodgson, Kirsty
Orozco-Moreno, Margarita
Scott, Emma
Garnham, Rebecca
Livermore, Karen
Thomas, Huw
Zhou, Yuhan
He, Jiepei
Bermudez, Abel
Garcia Marques, Fernando Jose
Bastian, Kayla
Hysenaj, Gerald
Archer Goode, Emily
Heer, Rakesh
Pitteri, Sharon
Wang, Ning
Elliott, David J.
Munkley, Jennifer
Source :
Scientific Reports; 11/18/2023, Vol. 13 Issue 1, p1-12, 12p
Publication Year :
2023

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20452322
Volume :
13
Issue :
1
Database :
Complementary Index
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
173738426
Full Text :
https://doi.org/10.1038/s41598-023-43019-8