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Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone

Hodgson, Kirsty, Orozco-Moreno, Margarita, Goode, Emily Archer, Fisher, Matthew, Garnham, Rebecca, Beatson, Richard, Turner, Helen, Livermore, Karen, Zhou, Yuhan, Wilson, Laura, Visser, Eline A, Pijnenborg, Johan FA, Eerden, Nienke, Moons, Sam J, Rossing, Emiel, Hysenaj, Gerald, Krishna, Rashi, Peng, Ziqian, Nangkana, Kyla Putri, Schmidt, Edward N, Duxfield, Adam, Dennis, Ella P, Heer, Rakesh, Lawson, Michelle A, Macauley, Matthew, Elliott, David J, Büll, Christian, Scott, Emma, Boltje, Thomas J, Drake, Richard R, Wang, Ning and Munkley, Jennifer (2024) Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone. eBioMedicine, 104 (105163). ISSN 2352-3964

Item Type: Article



Bone metastasis is a common consequence of advanced prostate cancer. Bisphosphonates can be used to manage symptoms, but there are currently no curative treatments available. Altered tumour cell glycosylation is a hallmark of cancer and is an important driver of a malignant phenotype. In prostate cancer, the sialyltransferase ST6GAL1 is upregulated, and studies show ST6GAL1-mediated aberrant sialylation of N-glycans promotes prostate tumour growth and disease progression.


Here, we monitor ST6GAL1 in tumour and serum samples from men with aggressive prostate cancer and using in vitro and in vivo models we investigate the role of ST6GAL1 in prostate cancer bone metastasis.


ST6GAL1 is upregulated in patients with prostate cancer with tumours that have spread to the bone and can promote prostate cancer bone metastasis in vivo. The mechanisms involved are multi-faceted and involve modification of the pre-metastatic niche towards bone resorption to promote the vicious cycle, promoting the development of M2 like macrophages, and the regulation of immunosuppressive sialoglycans. Furthermore, using syngeneic mouse models, we show that inhibiting sialylation can block the spread of prostate tumours to bone.


Our study identifies an important role for ST6GAL1 and α2-6 sialylated N-glycans in prostate cancer bone metastasis, provides proof-of-concept data to show that inhibiting sialylation can suppress the spread of prostate tumours to bone, and highlights sialic acid blockade as an exciting new strategy to develop new therapies for patients with advanced prostate cancer.

Available under License Creative Commons Attribution.

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Depositing User: Rebecca Garnham


Item ID: 17673
Identification Number:
ISSN: 2352-3964
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Catalogue record

Date Deposited: 29 May 2024 08:12
Last Modified: 29 May 2024 08:12


Author: Kirsty Hodgson
Author: Margarita Orozco-Moreno
Author: Emily Archer Goode
Author: Matthew Fisher
Author: Rebecca Garnham
Author: Richard Beatson
Author: Helen Turner
Author: Karen Livermore
Author: Yuhan Zhou
Author: Laura Wilson
Author: Eline A Visser
Author: Johan FA Pijnenborg
Author: Nienke Eerden
Author: Sam J Moons
Author: Emiel Rossing
Author: Gerald Hysenaj
Author: Rashi Krishna
Author: Ziqian Peng
Author: Kyla Putri Nangkana
Author: Edward N Schmidt
Author: Adam Duxfield
Author: Ella P Dennis
Author: Rakesh Heer
Author: Michelle A Lawson
Author: Matthew Macauley
Author: David J Elliott
Author: Christian Büll
Author: Emma Scott
Author: Thomas J Boltje
Author: Richard R Drake
Author: Ning Wang
Author: Jennifer Munkley

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine


Sciences > Biomedical Sciences
Sciences > Health Sciences

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