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The role of GCNT1 mediated O-glycosylation in aggressive prostate cancer.
Hodgson, Kirsty; Orozco-Moreno, Margarita; Scott, Emma; Garnham, Rebecca; Livermore, Karen; Thomas, Huw; Zhou, Yuhan; He, Jiepei; Bermudez, Abel; Garcia Marques, Fernando Jose; Bastian, Kayla; Hysenaj, Gerald; Archer Goode, Emily; Heer, Rakesh; Pitteri, Sharon; Wang, Ning; Elliott, David J; Munkley, Jennifer.
Afiliación
  • Hodgson K; Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
  • Orozco-Moreno M; Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
  • Scott E; Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
  • Garnham R; Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
  • Livermore K; Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
  • Thomas H; Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Paul O'Gorman Building, Newcastle upon Tyne, NE2 4HH, UK.
  • Zhou Y; Department of Oncology and Metabolism, The Mellanby Centre for Musculoskeletal Research, The University of Sheffield, Sheffield, UK.
  • He J; Department of Oncology and Metabolism, The Mellanby Centre for Musculoskeletal Research, The University of Sheffield, Sheffield, UK.
  • Bermudez A; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, Palo Alto, CA, 94304, USA.
  • Garcia Marques FJ; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, Palo Alto, CA, 94304, USA.
  • Bastian K; Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
  • Hysenaj G; Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
  • Archer Goode E; Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
  • Heer R; Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Paul O'Gorman Building, Newcastle upon Tyne, NE2 4HH, UK.
  • Pitteri S; Department of Urology, Freeman Hospital, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK.
  • Wang N; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, Palo Alto, CA, 94304, USA.
  • Elliott DJ; Department of Oncology and Metabolism, The Mellanby Centre for Musculoskeletal Research, The University of Sheffield, Sheffield, UK.
  • Munkley J; Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, NE1 3BZ, UK.
Sci Rep ; 13(1): 17031, 2023 10 09.
Article en En | MEDLINE | ID: mdl-37813880
ABSTRACT
Prostate cancer is the most common cancer in men and a major cause of cancer related deaths worldwide. Nearly all affected men develop resistance to current therapies and there is an urgent need to develop new treatments for advanced disease. Aberrant glycosylation is a common feature of cancer cells implicated in all of the hallmarks of cancer. A major driver of aberrant glycosylation in cancer is the altered expression of glycosylation enzymes. Here, we show that GCNT1, an enzyme that plays an essential role in the formation of core 2 branched O-glycans and is crucial to the final definition of O-glycan structure, is upregulated in aggressive prostate cancer. Using in vitro and in vivo models, we show GCNT1 promotes the growth of prostate tumours and can modify the glycome of prostate cancer cells, including upregulation of core 2 O-glycans and modifying the O-glycosylation of secreted glycoproteins. Furthermore, using RNA sequencing, we find upregulation of GCNT1 in prostate cancer cells can alter oncogenic gene expression pathways important in tumour growth and metastasis. Our study highlights the important role of aberrant O-glycosylation in prostate cancer progression and provides novel insights regarding the mechanisms involved.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Límite: Humans / Male Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Límite: Humans / Male Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido