Gu Yuchao, Gao Jiangang, Han Cuifang, Zhang Xinling, Liu Haiyan, Ma Leina, Sun Xiaoqing, Yu Wengong
Key Laboratory of Marine Drugs, Chinese Ministry of Education, Key Laboratory of Glycoscience and Glycotechnology of Shandong Province, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, P.R. China.
Department of Urology Surgery, Qingdao Municipal Hospital, Qingdao 266011, P.R. China.
Mol Med Rep. 2014 Aug;10(2):897-904. doi: 10.3892/mmr.2014.2269. Epub 2014 May 26.
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.
O-连接的β-N-乙酰葡糖胺（O-GlcNAc）是一种连接在众多细胞质和核蛋白中丝氨酸或苏氨酸残基侧链羟基上的O-连接β-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O-GlcNAc的水平，发现与相应的相邻组织相比，前列腺癌组织中整体的O-GlcNAc修饰（也称为O-GlcNAc糖基化）显著增加。此外，我们发现前列腺癌细胞中整体的O-GlcNAc糖基化增加，而良性前列腺增生（BPH）上皮细胞中则没有。O-GlcNAc增强了前列腺癌细胞的非锚定依赖性生长以及迁移/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糖基化增加会诱导非致瘤性（BPH）细胞发生恶性转化。此外，我们的研究表明，抑制E-钙黏蛋白/连环蛋白/细胞骨架复合物的形成可能是O-GlcNAc诱导前列腺癌进展的基础。总体而言，这些发现表明，O-GlcNAc糖基化在前列腺癌组织中增加，而在肝癌和胰腺癌组织中未增加，并且O-GlcNAc可以增强前列腺癌细胞的恶性程度。
