Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growthMore about Open Access at the Crick
Authors listEmma Scott Kirsty Hodgson Bea 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 Ben Schumann Jennifer Munkley
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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.
Issue number 12