s41388-023-02604-x (1).pdf (9.36 MB)
Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth.
journal contributionposted on 2023-03-22, 11:00 authored by Emma Scott, Kirsty Hodgson, Beatriz Calle, Helen Turner, Kathleen Cheung, Abel Bermudez, Fernando Jose Garcia Marques, Hayley Pye, Edward Christopher Yo, Khirul Islam, Htoo Zarni Oo, Urszula L McClurg, Laura Wilson, Huw Thomas, Fiona M Frame, Margarita Orozco-Moreno, Kayla Bastian, Hector M Arredondo, Chloe Roustan, Melissa Anne Gray, Lois Kelly, Aaron Tolson, Ellie Mellor, Gerald Hysenaj, Emily Archer Goode, Rebecca Garnham, Adam Duxfield, Susan Heavey, Urszula Stopka-Farooqui, Aiman Haider, Alex Freeman, Saurabh Singh, Edward W Johnston, Shonit Punwani, Bridget Knight, Paul McCullagh, John McGrath, Malcolm Crundwell, Lorna Harries, Denisa Bogdan, Daniel Westaby, Gemma Fowler, Penny Flohr, Wei Yuan, Adam Sharp, Johann de Bono, Norman J Maitland, Simon Wisnovsky, Carolyn R Bertozzi, Rakesh Heer, Ramon Hurtado Guerrero, Mads Daugaard, Janne Leivo, Hayley Whitaker, Sharon Pitteri, Ning Wang, David J Elliott, Benjamin Schumann, Jennifer Munkley
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.