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Updated: Jul 14, 2025

Bioinformatics Resources for the Study of Glycan-Mediated Protein Interactions
Published on: January 20, 2022
The role of GCNT1 mediated O-glycosylation in aggressive prostate cancer
Kirsty Hodgson1, Margarita Orozco-Moreno1, Emma Scott1
1Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
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.
Insights
Aggressive prostate cancer shows increased levels of the GCNT1 enzyme, which drives tumor growth and metastasis. Targeting GCNT1 may offer new therapeutic strategies for advanced prostate cancer.
Area of Science:
- Oncology
- Glycobiology
- Biochemistry
Background:
- Prostate cancer is a leading cause of cancer death globally, with limited treatment options for advanced stages.
- Therapeutic resistance is common in prostate cancer, necessitating the development of novel treatment strategies.
- Aberrant glycosylation, driven by altered glycosylation enzymes, is a hallmark of cancer, influencing tumor progression.
Purpose of the Study:
- To investigate the role of the glycosylation enzyme GCNT1 in prostate cancer progression.
- To explore how GCNT1 influences the cellular glycome and oncogenic pathways in prostate cancer.
Main Methods:
- In vitro and in vivo experimental models of prostate cancer.
- Analysis of GCNT1 expression levels in aggressive prostate cancer.
- RNA sequencing to assess gene expression alterations.
- Glycomic analysis of prostate cancer cells and secreted glycoproteins.
Main Results:
- GCNT1 is upregulated in aggressive prostate cancer.
- GCNT1 promotes prostate tumor growth and modifies the cancer cell glycome, including core 2 O-glycans.
- Upregulation of GCNT1 alters oncogenic gene expression pathways linked to tumor growth and metastasis.
Conclusions:
- Aberrant O-glycosylation, mediated by GCNT1, plays a significant role in prostate cancer progression.
- GCNT1 represents a potential therapeutic target for advanced prostate cancer.
- This study provides new mechanistic insights into the role of glycosylation in prostate cancer.
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