Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability.
Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability.
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DOI：
10.1016/j.ebiom.2016.04.018
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发表时间：
2016-06
期刊：
影响因子：
11.1
通讯作者：
Elliott DJ
中科院分区：
文献类型：
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作者：
Munkley J;Vodak D;Livermore KE;James K;Wilson BT;Knight B;Mccullagh P;Mcgrath J;Crundwell M;Harries LW;Leung HY;Robson CN;Mills IG;Rajan P;Elliott DJ
类固醇雄激素在前列腺癌的进展和治疗中起着关键作用，雄激素剥夺疗法是用于控制癌症生长的一线治疗。在这里，我们应用一种新的搜索策略，以确定雄激素调节的细胞通路，可能是临床上重要的前列腺癌。使用RNASeq数据，我们搜索了在培养中对急性雄激素刺激和前列腺癌患者雄激素剥夺反应中表现出相互表达变化的基因。在700个显示相互表达模式的基因中，我们观察到细胞过程糖基化的显著富集。在31种相互调节的糖基化酶中，一组8种（GALNT 7、ST 6 GalNAc 1、GCNT 1、UAP 1、PGM 3、CSGALNACT 1、ST 6 GAL 1和EDEM 3）在临床前列腺癌中显著上调。雄激素暴露刺激了这组核心调节酶下游聚糖结构的合成，包括唾液酸-Tn（sTn）、唾液酸LewisX（SLeX）、O-GlcNAc和硫酸软骨素，表明雄激素对这组核心酶的调节控制了聚糖合成的关键步骤。这些酶中的每一种的表达也有助于前列腺癌细胞活力。这项研究确定糖基化是雄激素控制的一个全球目标，并表明特定糖基化酶的丢失可能有助于雄激素耗竭治疗后肿瘤消退。前列腺癌细胞系和7名前列腺癌患者的RNA测序鉴定了700个临床相关雄激素调节基因的核心组。糖基化是前列腺癌细胞中雄激素控制的一个全局目标。一组8种糖基化酶对前列腺癌细胞活力很重要。
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. RNA-sequencing of a prostate cancer cell line and 7 prostate cancer patients identifies a core set of 700 clinically relevant androgen-regulated genes. Glycosylation is a global target for androgen control in prostate cancer cells. A set of 8 glycosylation enzymes are important for prostate cancer cell viability.