Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer.
Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer. Amongst 700 genes displaying reciprocal expression patterns we observed a significant enrichment in the cellular process glycosylation. Of 31 reciprocally-regulated glycosylation enzymes, a set of 8 (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3) were significantly up-regulated in clinical prostate carcinoma. Androgen exposure stimulated synthesis of glycan structures downstream of this core set of regulated enzymes including sialyl-Tn (sTn), sialyl Lewis(X) (SLe(X)), O-GlcNAc and chondroitin sulphate, suggesting androgen regulation of the core set of enzymes controls key steps in glycan synthesis. Expression of each of these enzymes also contributed to prostate cancer cell viability. This study identifies glycosylation as a global target for androgen control, and suggests loss of specific glycosylation enzymes might contribute to tumour regression following androgen depletion therapy.
EBioMedicine. 2016 Apr 20 [Epub]
Jennifer Munkley, Daniel Vodak, Karen E Livermore, Katherine James, Brian T Wilson, Bridget Knight, Paul Mccullagh, John Mcgrath, Malcolm Crundwell, Lorna W Harries, Hing Y Leung, Craig N Robson, Ian G Mills, Prabhakar Rajan, David J Elliott
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK. Electronic address: ., Bioinformatics Core Facility, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway., Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK., Interdisciplinary Computing and Complex BioSystems Research Group, Newcastle University, Newcastle upon Tyne, UK., Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK; Northern Genetics Service, Newcastle Upon Tyne NHS Foundation Trust, International Centre for Life, Newcastle upon Tyne, UK., NIHR Exeter Clinical Research Facility, RD&E NHS Foundation Trust, UK., Department of Pathology, RD&E NHS Foundation Trust, UK., Exeter Surgical Health Services Research Unit, RD&E NHS Foundation Trust, UK., Department of Urology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK., Institute of Biomedical and Clinical Sciences, University of Exeter, Devon EX1 2LU, UK., Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G12 8QQ, UK., Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK., Prostate Cancer Research Group, Centre for Molecular Medicine Norway (NCMM), University of Oslo and Oslo University Hospitals, Oslo, Norway; Departments of Molecular Oncology, Institute of Cancer Research and Radium Hospital, Oslo, Norway; PCUK/Movember Centre of Excellence for Prostate Cancer Research, Centre for Cancer Research and Cell Biology (CCRCB), Queen's University, Belfast, UK., Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK., Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/27428423
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