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

Abstract

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.

Metadata

Authors/Creators:

Scott, E.
Hodgson, K.
Calle, B. https://orcid.org/0000-0002-9893-9803
Turner, H.
Cheung, K.
Bermudez, A.
Marques, F.J.G.
Pye, H. https://orcid.org/0000-0001-7042-5416
Yo, E.C.
Islam, K.
Oo, H.Z.
McClurg, U.L.
Wilson, L.
Thomas, H.
Frame, F.M.
Orozco-Moreno, M.
Bastian, K.
Arredondo, H.M.
Roustan, C.
Gray, M.A.
Kelly, L.
Tolson, A.
Mellor, E.
Hysenaj, G.
Goode, E.A.
Garnham, R.
Duxfield, A.
Heavey, S.
Stopka-Farooqui, U.
Haider, A.
Freeman, A.
Singh, S.
Johnston, E.W.
Punwani, S.
Knight, B.
McCullagh, P.
McGrath, J.
Crundwell, M.
Harries, L.
Bogdan, D.
Westaby, D.
Fowler, G.
Flohr, P.
Yuan, W.
Sharp, A. https://orcid.org/0000-0002-3740-1612
de Bono, J.
Maitland, N.J. https://orcid.org/0000-0003-1607-9035
Wisnovsky, S.
Bertozzi, C.R. https://orcid.org/0000-0003-4482-2754
Heer, R.
Guerrero, R.H. https://orcid.org/0000-0002-3122-9401
Daugaard, M.
Leivo, J.
Whitaker, H. https://orcid.org/0000-0002-2695-0202
Pitteri, S. https://orcid.org/0000-0002-3119-873X
Wang, N. https://orcid.org/0000-0002-2663-7515
Elliott, D.J.
Schumann, B. https://orcid.org/0000-0001-5504-0147
Munkley, J. https://orcid.org/0000-0002-8631-4531

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Keywords:

Cell growth; Diagnostic markers; Glycobiology; Prostate cancer

Dates: