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Lookup NU author(s): Dr Emma ScottORCiD, Emily Archer Goode, Rebecca Garnham, Dr Kirsty Hodgson, Maggie Orozco Moreno, Karen Livermore, Kyla Putri Nangkana, Laura WilsonORCiD, Huw ThomasORCiD, Adriana Buskin, Dr Anastasia Hepburn, Adam Duxfield, Kayla Bastian, Dr Gerald Hysenaj, Professor Rakesh Heer, Dr Jennifer Munkley
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX-Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Author(s): Scott E, Archer Goode E, Garnham R, Hodgson K, Orozco-Moreno M, Turner H, Livermore K, Putri Nangkana K, Frame FM, Bermudez A, Garcia Marques FJ, McClurg UL, Wilson L, Thomas H, Buskin A, Hepburn A, Duxfield A, Bastian K, Pye H, Arredondo HM, Hysenaj G, Heavey S, Stopka-Farooqui U, Haider A, Freeman A, Singh S, Johnston EW, Punwani S, Knight B, McCullagh P, McGrath J, Crundwell M, Harries L, Heer R, Maitland NJ, Whitaker H, Pitteri S, Troyer DA, Wang N, Elliott DJ, Drake RR, Munkley J
Publication type: Article
Publication status: Published
Journal: Journal of Pathology
Year: 2023
Volume: 261
Issue: 1
Pages: 71-84
Print publication date: 01/09/2023
Online publication date: 07/08/2023
Acceptance date: 02/06/2023
Date deposited: 18/09/2023
ISSN (print): 0022-3417
ISSN (electronic): 1096-9896
Publisher: John Wiley and Sons Ltd
URL: https://doi.org/10.1002/path.6152
DOI: 10.1002/path.6152
PubMed id: 37550801
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