Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)

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




Julkaisun tekijätScott Emma, Hodgson Kirsty, Calle Beatriz, Turner Helen, Cheung Kathleen, Bermudez Abel, Marques Fernando Jose Garcia, Pye Hayley, Yo Edward Christopher, Islam Khirul, Oo Htoo Zarni, McClurg Urszula L., Wilson Laura, Thomas Huw, Frame Fiona M., Orozco-Moreno Margarita, Bastian Kayla, Arredondo Hector M., Roustan Chloe, Gray Melissa Anne, Kelly Lois, Tolson Aaron, Mellor Ellie, Hysenaj Gerald, Goode Emily Archer, Garnham Rebecca, Duxfield Adam, Heavey Susan, Stopka-Farooqui Urszula, Haider Aiman, Freeman Alex, Singh Saurabh, Johnston Edward W., Punwani Shonit, Knight Bridget, McCullagh Paul, McGrath John, Crundwell Malcolm, Harries Lorna, Bogdan Denisa, Westaby Daniel, Fowler Gemma, Flohr Penny, Yuan Wei, Sharp Adam, de Bono Johann, Maitland Norman J., Wisnovsky Simon, Bertozzi Carolyn R., Heer Rakesh, Guerrero Ramon Hurtado, Daugaard Mads, Leivo Janne, Whitaker Hayley, Pitteri Sharon, Wang Ning, Elliott David J., Schumann Benjamin, Munkley Jennifer

KustantajaNature Publishing Group

Julkaisuvuosi2023

JournalOncogene

Tietokannassa oleva lehden nimiOncogene

Lehden akronyymiOncogene

Volyymi42

Aloitussivu926

Lopetussivun numero937

ISSN0950-9232

eISSN1476-5594

DOIhttp://dx.doi.org/10.1038/s41388-023-02604-x

Verkko-osoitehttps://www.nature.com/articles/s41388-023-02604-x

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/178407096


Tiivistelmä
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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Last updated on 2023-03-08 at 10:25