O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy of prostate cancer cells
O-GlcNAcylation is increased in prostate cancer tissues and enhances malignancy of prostate cancer cells
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O-GlcNAc 酰化在前列腺癌组织中增加并增强前列腺癌细胞的恶性程度。
DOI：
10.3892/mmr.2014.2269
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发表时间：
2014-08-01
影响因子：
3.4
通讯作者：
Yu, Wengong
中科院分区：
文献类型：
--
作者：
Gu, Yuchao;Gao, Jiangang;Yu, Wengong
O-GlcNAc 是连接到许多细胞质和核蛋白中丝氨酸或苏氨酸残基的侧链羟基上的 O-连接 α-N-乙酰葡糖胺部分。在本研究中，我们检测了前列腺癌、肝癌和胰腺癌组织中的O-GlcNAc水平，发现与相应的邻近组织相比，整体O-GlcNAc修饰（也称为O-GlcNAcylation）在前列腺癌组织中特异性增加。此外，我们发现前列腺癌细胞中整体 O-GlcNAc 酰化增加，而良性前列腺增生 (BPH) 上皮细胞中则没有增加。 O-GlcNAc 增强了前列腺癌细胞的非贴壁依赖性生长和迁移/侵袭能力。更重要的是，据我们所知，我们首次在此提供直接证据，证明O-GlcNAc糖基化的增加会诱导非致瘤（BPH）细胞的恶性转化。此外，我们的研究表明，抑制 E-钙粘蛋白/连环蛋白/细胞骨架复合物的形成可能是 O-GlcNAc 诱导的前列腺癌进展的基础。总的来说，这些发现表明O-GlcNAc在前列腺癌组织中增加，但在肝癌和胰腺癌组织中没有增加，并且O-GlcNAc可以增强前列腺癌细胞的恶性程度。
O-GlcNAc is an O-linked ?-N-acetylglucosamine moiety attached to the side-chain hydroxyl of a serine or threonine residue in numerous cytoplasmic and nuclear proteins. In this study, we detected the level of O-GlcNAc in prostate, liver and pancreatic cancer tissues, and found that the global O-GlcNAc modification also known as O-GlcNAcylation, is specifically increased in prostate cancer tissues compared to corresponding adjacent tissues. In addition, we found that global O-GlcNAcylation is increased in prostate cancer cells and not in benign prostatic hyperplasia (BPH) epithelial cells. O-GlcNAc enhanced the anchorage-independent growth and the migratory/invasive ability of prostate cancer cells. More importantly, we provide here, for the first time to the best of our knowledge, direct evidence that increased O-GlcNAcylation induces malignant transformation of nontumorigenic (BPH) cells. Furthermore, our study suggested that inhibiting the formation of the E-cadherin/catenin/cytoskeleton complex may underly the O-GlcNAc-induced prostate cancer progression. Overall, these findings indicated that O-GlcNAcylation is increased in prostate, but not in liver and pancreatic cancer tissues, and that O-GlcNAc can enhance the malignancy of prostate cancer cells.