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.

Metadata

Item Type:	Article
Authors/Creators:	Scott, E. Hodgson, K. Calle, B. https://orcid.org/0000-0002-9893-9803 Turner, H. Cheung, K. Bermudez, A. Marques, F.J.G. Pye, H. https://orcid.org/0000-0001-7042-5416 Yo, E.C. Islam, K. Oo, H.Z. McClurg, U.L. Wilson, L. Thomas, H. Frame, F.M. Orozco-Moreno, M. Bastian, K. Arredondo, H.M. Roustan, C. Gray, M.A. Kelly, L. Tolson, A. Mellor, E. Hysenaj, G. Goode, E.A. Garnham, R. Duxfield, A. Heavey, S. Stopka-Farooqui, U. Haider, A. Freeman, A. Singh, S. Johnston, E.W. Punwani, S. Knight, B. McCullagh, P. McGrath, J. Crundwell, M. Harries, L. Bogdan, D. Westaby, D. Fowler, G. Flohr, P. Yuan, W. Sharp, A. https://orcid.org/0000-0002-3740-1612 de Bono, J. Maitland, N.J. https://orcid.org/0000-0003-1607-9035 Wisnovsky, S. Bertozzi, C.R. https://orcid.org/0000-0003-4482-2754 Heer, R. Guerrero, R.H. https://orcid.org/0000-0002-3122-9401 Daugaard, M. Leivo, J. Whitaker, H. https://orcid.org/0000-0002-2695-0202 Pitteri, S. https://orcid.org/0000-0002-3119-873X Wang, N. https://orcid.org/0000-0002-2663-7515 Elliott, D.J. Schumann, B. https://orcid.org/0000-0001-5504-0147 Munkley, J. https://orcid.org/0000-0002-8631-4531
Copyright, Publisher and Additional Information:	© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords:	Cell growth; Diagnostic markers; Glycobiology; Prostate cancer
Dates:	Published: 16 March 2023 Published (online): 1 February 2023 Accepted: 19 January 2023
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield)
Funding Information:	Funder Grant number WELLCOME TRUST (THE) UNSPECIFIED PROSTATE CANCER RESEARCH 6961 PROSTATE CANCER UK RIA21-ST2-006
Depositing User:	Symplectic Sheffield
Date Deposited:	21 Mar 2023 15:21
Last Modified:	21 Mar 2023 15:21
Published Version:	http://dx.doi.org/10.1038/s41388-023-02604-x
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1038/s41388-023-02604-x
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:197526

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Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth

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