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

Jennifer Munkley

doi:10.1038/s41388-023-02604-x

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

Jennifer Munkley

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Number of pages	12
Journal	Oncogene
Early online date	1 Feb 2023
DOIs	https://doi.org/10.1038/s41388-023-02604-x
Publication status	E-pub ahead of print - 1 Feb 2023

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@article{96748d2065794f65b124640716d8cf74,

title = "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.",

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

note = "{\textcopyright} The Author(s) 2023.",

year = "2023",

month = feb,

day = "1",

doi = "10.1038/s41388-023-02604-x",

language = "English",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

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TY - JOUR

T1 - Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth

AU - Jennifer Munkley

AU - Scott, Emma

AU - Hodgson, Kirsty

AU - Calle, Beatriz

AU - Turner, Helen

AU - Cheung, Kathleen

AU - Bermudez, Abel

AU - Marques, Fernando Jose Garcia

AU - Pye, Hayley

AU - Yo, Edward Christopher

AU - Islam, Khirul

AU - Oo, Htoo Zarni

AU - McClurg, Urszula L

AU - Wilson, Laura

AU - Thomas, Huw

AU - Frame, Fiona M

AU - Orozco-Moreno, Margarita

AU - Bastian, Kayla

AU - Arredondo, Hector M

AU - Roustan, Chloe

AU - Gray, Melissa Anne

AU - Kelly, Lois

AU - Tolson, Aaron

AU - Mellor, Ellie

AU - Hysenaj, Gerald

AU - Goode, Emily Archer

AU - Garnham, Rebecca

AU - Duxfield, Adam

AU - Heavey, Susan

AU - Stopka-Farooqui, Urszula

AU - Haider, Aiman

AU - Freeman, Alex

AU - Singh, Saurabh

AU - Johnston, Edward W

AU - Punwani, Shonit

AU - Knight, Bridget

AU - McCullagh, Paul

AU - McGrath, John

AU - Crundwell, Malcolm

AU - Harries, Lorna

AU - Bogdan, Denisa

AU - Westaby, Daniel

AU - Fowler, Gemma

AU - Flohr, Penny

AU - Yuan, Wei

AU - Sharp, Adam

AU - de Bono, Johann

AU - Maitland, Norman J

AU - Wisnovsky, Simon

AU - Bertozzi, Carolyn R

AU - Munkley, Jennifer

PY - 2023/2/1

Y1 - 2023/2/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41388-023-02604-x

DO - 10.1038/s41388-023-02604-x

M3 - Article

C2 - 36725887

SN - 0950-9232

JO - Oncogene

JF - Oncogene

ER -