Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability

Munkley, Jennifer, Vodak, Daniel, Livermore, Karen E., James, Katherine, Wilson, Brian T., Knight, Bridget, Mccullagh, Paul, Mcgrath, John, Crundwell, Malcolm, Harries, Lorna W., Leung, Hing Y., Robson, Craig N., Mills, Ian G., Rajan, Prabhakar and Elliott, David J. (2016) Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability. EBioMedicine, 8. pp. 103-116. ISSN 2352-3964

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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, 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 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.

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