Glycosylation is an androgen-regulated process essential for prostate cancer cell viability

2.50
Hdl Handle:
http://hdl.handle.net/11287/607243
Title:
Glycosylation is an androgen-regulated process essential for prostate cancer cell viability
Authors:
Munkley, J.; Vodak, D.; Livermore, K. E.; James, K.; Wilson, B. T.; Knight, Bridget A.; McCullagh, Paul; McGrath, John S; Crundwell, Malcolm; Harries, L. W.; Leung, H. Y.; Robson, C. N.; Mills, I. G.; Rajan, P.; Elliott, D. J.
Abstract:
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, GCNT, 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 LewisX (SLeX), 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.
Citation:
Glycosylation is an androgen-regulated process essential for prostate cancer cell viability. 2016. 8:103-16. EBioMedicine.
Publisher:
Elsevier
Journal:
EBioMedicine
Issue Date:
20-Apr-2016
URI:
http://hdl.handle.net/11287/607243
DOI:
10.1016/j.ebiom.2016.04.018
Additional Links:
http://www.sciencedirect.com/science/article/pii/S2352396416301530
Note:
This article is freely available via Open Access. Click on the link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
Appears in Collections:
Urology; HeSRU publications; Exeter Clinical Laboratory International (Blood Sciences, Genetics, Cellular Pathology & Microbiology); 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMunkley, J.en
dc.contributor.authorVodak, D.en
dc.contributor.authorLivermore, K. E.en
dc.contributor.authorJames, K.en
dc.contributor.authorWilson, B. T.en
dc.contributor.authorKnight, Bridget A.en
dc.contributor.authorMcCullagh, Paulen
dc.contributor.authorMcGrath, John Sen
dc.contributor.authorCrundwell, Malcolmen
dc.contributor.authorHarries, L. W.en
dc.contributor.authorLeung, H. Y.en
dc.contributor.authorRobson, C. N.en
dc.contributor.authorMills, I. G.en
dc.contributor.authorRajan, P.en
dc.contributor.authorElliott, D. J.en
dc.date.accessioned2016-04-27T14:22:39Zen
dc.date.available2016-04-27T14:22:39Zen
dc.date.issued2016-04-20en
dc.identifier.citationGlycosylation is an androgen-regulated process essential for prostate cancer cell viability. 2016. 8:103-16. EBioMedicine.en
dc.identifier.doi10.1016/j.ebiom.2016.04.018en
dc.identifier.urihttp://hdl.handle.net/11287/607243en
dc.description.abstractSteroid 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, GCNT, 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 LewisX (SLeX), 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.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S2352396416301530en
dc.rightsArchived with thanks to EBioMedicine. Available as Open Access under Creative Commons licence. This is a PDF file of an unedited manuscript that has been accepted for publication. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.en
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.en
dc.titleGlycosylation is an androgen-regulated process essential for prostate cancer cell viabilityen
dc.typeJournal Articleen
dc.identifier.journalEBioMedicineen
dc.description.noteThis article is freely available via Open Access. Click on the link above to access the full-text via the publisher's site.en
dc.description.fundingThis work was funded by Prostate Cancer UK (PG12-34), The J. G. W Patterson Foundation, The Wellcome Trust (grant numbers WT080368MA and WT089225/Z/09/Z), BBSRC (grant BB/1006923/1 and BB/J007293/1) and Breast Cancer Now (grant number 2014NovPR355)en
dc.type.versionIn press (epub ahead of print)en
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