Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth
- PMID: 36725887
- PMCID: PMC10020086
- DOI: 10.1038/s41388-023-02604-x
Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth
Abstract
Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression.
© 2023. The Author(s).
Conflict of interest statement
JM is shareholder and Scientific Advisor of GlycoScoreDx Ltd. ES and GH are shareholders of GlycoScoreDx Ltd. The authors have filed a patent relating to this work (GB Patent GB2,594,103). CRB is a cofounder and scientific advisory board member of Lycia Therapeutics, Palleon Pharmaceuticals, EnableBioscience, Redwood Biosciences (a subsidiary of Catalent), OliLux Bio, Grace Science LLC, and InterVenn Biosciences. The other authors declare no competing interests.
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Comment in
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The role of GALNT7 as a potential diagnostic marker in prostate cancer.Nat Rev Urol. 2023 Apr;20(4):198. doi: 10.1038/s41585-023-00756-9. Nat Rev Urol. 2023. PMID: 36918685 No abstract available.
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Temporary cessation versus continued TKI therapy for RCC.Nat Rev Urol. 2023 Apr;20(4):198. doi: 10.1038/s41585-023-00755-w. Nat Rev Urol. 2023. PMID: 36922603 No abstract available.
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