Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth.
Creators: name: Scott, Emma
name: Hodgson, Kirsty
name: Calle, Beatriz
name: Turner, Helen
name: Cheung, Kathleen
name: Bermudez, Abel
name: Marques, Fernando Jose Garcia
name: Pye, Hayley
name: Yo, Edward Christopher
name: Islam, Khirul
name: Oo, Htoo Zarni
name: McClurg, Urszula L
name: Wilson, Laura
name: Thomas, Huw
name: Frame, Fiona M
name: Orozco-Moreno, Margarita
name: Bastian, Kayla
name: Arredondo, Hector M
name: Roustan, Chloe
name: Gray, Melissa Anne
name: Kelly, Lois
name: Tolson, Aaron
name: Mellor, Ellie
name: Hysenaj, Gerald
name: Goode, Emily Archer
name: Garnham, Rebecca
name: Duxfield, Adam
name: Heavey, Susan
name: Stopka-Farooqui, Urszula
name: Haider, Aiman
name: Freeman, Alex
name: Singh, Saurabh
name: Johnston, Edward W
name: Punwani, Shonit
name: Knight, Bridget
name: McCullagh, Paul
name: McGrath, John
name: Crundwell, Malcolm
name: Harries, Lorna
name: Bogdan, Denisa
name: Westaby, Daniel
name: Fowler, Gemma
name: Flohr, Penny
name: Yuan, Wei
name: Sharp, Adam
name: de Bono, Johann
name: Maitland, Norman J
name: Wisnovsky, Simon
name: Bertozzi, Carolyn R
name: Heer, Rakesh
name: Guerrero, Ramon Hurtado
name: Daugaard, Mads
name: Leivo, Janne
name: Whitaker, Hayley
name: Pitteri, Sharon
name: Wang, Ning
name: Elliott, David J
name: Schumann, Benjamin
name: Munkley, Jennifer
Publisher: name: The Francis Crick Institute
Year: 2023
Subjects: classificationCode: Biochemistry & Proteomics
subject: Biochemistry &amp; Proteomics
classificationCode: Synthetic Biology
subject: Synthetic Biology
classificationCode: Tumour Biology
subject: Tumour Biology
classificationCode: Structural Biology & Biophysics
subject: Structural Biology &amp; Biophysics
classificationCode: Cell Biology
subject: Cell Biology
classificationCode: Chemical Biology & High Throughput
subject: Chemical Biology &amp; High Throughput
classificationCode: Metabolism
subject: Metabolism

description: 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.