The role of GCNT1 mediated O-glycosylation in aggressive prostate cancer
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Published:2023-10-09
Issue:1
Volume:13
Page:
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ISSN:2045-2322
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Container-title:Scientific Reports
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language:en
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Short-container-title:Sci Rep
Author:
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 SharonORCID, Wang NingORCID, Elliott David J., Munkley Jennifer
Abstract
AbstractProstate 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.
Funder
Prostate Cancer Research
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
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