Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth. Emma Scott 1, Kirsty Hodgson 1, Beatriz Calle 2 3, Helen Turner 4, Kathleen Cheung 1, Abel Bermudez 5, Fernando Jose Garcia Marques 5, Hayley Pye 6, Edward Christopher Yo 1, Khirul Islam 7, Htoo Zarni Oo 8 9, Urszula L McClurg 10, Laura Wilson 11, Huw Thomas 11, Fiona M Frame 12, Margarita Orozco-Moreno 1, Kayla Bastian 1, Hector M Arredondo 13, Chloe Roustan 14, Melissa Anne Gray 15, Lois Kelly 1, Aaron Tolson 1, Ellie Mellor 1, Gerald Hysenaj 1, Emily Archer Goode 1, Rebecca Garnham 1, Adam Duxfield 1, Susan Heavey 6, Urszula Stopka-Farooqui 6, Aiman Haider 16, Alex Freeman 16, Saurabh Singh 17, Edward W Johnston 17, Shonit Punwani 17, Bridget Knight 18, Paul McCullagh 19, John McGrath 20, Malcolm Crundwell 20, Lorna Harries 21, Denisa Bogdan 22, Daniel Westaby 22 23, Gemma Fowler 22, Penny Flohr 22, Wei Yuan 22, Adam Sharp 22 23, Johann de Bono 22 23, Norman J Maitland 12, Simon Wisnovsky 24, Carolyn R Bertozzi 25, Rakesh Heer 11 26, Ramon Hurtado Guerrero 27 28, Mads Daugaard 8 9, Janne Leivo 7 29, Hayley Whitaker 6, Sharon Pitteri 5, Ning Wang 13, David J Elliott 1, Benjamin Schumann 2 3, Jennifer Munkley 30. Oncogene. 2023 Feb 1. doi: 10.1038/s41388-023-02604-x. Online ahead of print.

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.

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