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Lookup NU author(s): Maggie Orozco Moreno, Dr Kirsty Hodgson, Kayla Bastian, Emily Archer Goode, Dr Jennifer Munkley
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Aberrant glycosylation is a hallmark of cancer and is not just a consequence, but also a driver of a malignant phenotype. In prostate cancer, changes in fucosylated and sialylated glycans are common and this has important implications for tumor progression, metastasis, and immune evasion. Glycans hold huge translational potential and new therapies targeting tumor-associated glycans are currently being tested in clinical trials for several tumor types. Inhibitors targeting fucosylation and sialylation have been developed and show promise for cancer treatment, but translational development is hampered by safety issues related to systemic adverse effects. Recently, potent metabolic inhibitors of sialylation and fucosylation were designed that reach higher effective concentrations within the cell, thereby rendering them useful tools to study sialylation and fucosylation as potential candidates for therapeutic testing. Here, we investigated the effects of global metabolic inhibitors of fucosylation and sialylation in the context of prostate cancer progression. We find that these inhibitors effectively shut down the synthesis of sialylated and fucosylated glycans to remodel the prostate cancer glycome with only minor apparent side effects on other glycan types. Our results demonstrate that treatment with inhibitors targeting fucosylation or sialylation decreases prostate cancer cell growth and downregulates the expression of genes and proteins important in the trajectory of disease progression. We anticipate our findings will lead to the broader use of metabolic inhibitors to explore the role of fucosylated and sialylated glycans in prostate tumor pathology and may pave the way for the development of new therapies for prostate cancer.
Author(s): Orozco-Moreno M, Visser EA, Hodgson K, Hipgrave Ederveen AL, Bastian K, Archer Goode E, Öztürk O, Pijnenborg JFA, Eerden N, Moons SJ, Rossing E, Wang N, de Haan N, Büll C, Boltje TJ, Munkley J
Publication type: Article
Publication status: Published
Journal: Glycobiology
Year: 2023
Volume: 33
Issue: 12
Pages: 1155-1171
Print publication date: 01/12/2023
Online publication date: 17/10/2023
Acceptance date: 14/10/2023
Date deposited: 14/05/2024
ISSN (electronic): 1460-2423
Publisher: Oxford University Press
URL: https://doi.org/10.1093/glycob/cwad085
DOI: 10.1093/glycob/cwad085
PubMed id: 37847613
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