A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells
A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells
复制标题
卵巢癌细胞中 O-GlcNAc 酰化、迁移的改变与 E-钙粘蛋白水平变化之间的相关性
DOI：
10.1016/j.yexcr.2013.03.013
复制
发表时间：
2013-06-10
影响因子：
3.7
通讯作者：
Yang, Zhu
中科院分区：
文献类型：
--
作者：
Jin, Feng-zhen;Yu, Chao;Yang, Zhu
O-GlcNAc酰化是细胞核和细胞质蛋白质的动态和可逆的翻译后修饰。近年来，人们对O-GlcNAc化在多种恶性肿瘤中的作用进行了研究，发现O-GlcNAc化与肿瘤细胞的转移有关。在这项研究中，我们模拟了四种不同的卵巢癌细胞，并研究了O-GlcNAc化对卵巢癌细胞迁移的影响。我们发现，与OVCAR 3细胞相比，HO-8910 PM细胞中的总O-GlcNAc化水平升高。此外，通过OGT沉默或OGA抑制改变总O-GlcNAc化水平，我们发现PUGNAc和Thiamet G处理显著增强OVCAR 3细胞的迁移能力，而OGT沉默显著抑制HO-8910 PM细胞的迁移能力。此外，我们还发现，卵巢癌细胞中的O-GlcNAc化蛋白E-钙粘蛋白的表达在OVCAR 3细胞中通过OGA抑制而降低，在HO-8910 PM细胞中通过OGT沉默而升高。这些结果表明，O-GlcNAc化可以增强卵巢癌细胞的迁移能力，降低E-cadherin的表达。O-GlcNAc化可能成为卵巢癌治疗的另一个潜在靶点。(C)2013 Elsevier Inc. All rights reserved.
O-GlcNAcylation is a dynamic and reversible posttranslational modification of nuclear and cytoplasmic proteins. In recent years, the roles of O-GlcNAcylation in several human malignant tumors have been investigated, and O-GlcNAcylation was found to be linked to cellular features relevant to metastasis. In this study, we modeled four diverse ovarian cancer cells and investigated the effects of O-GlcNAcylation on ovarian cancer cell migration. We found that total O-GlcNAcylation level was elevated in HO-8910PM cells compared to OVCAR3 cells. Additionally, through altering the total O-GlcNAcylation level by OGT silencing or OGA inhibition, we found that the migration of OVCAR3 cells was dramatically enhanced by PUGNAc and Thiamet G treatment, and the migration ability of HO-8910PM cells was significantly inhibited by OGT silencing. Furthermore, we also found that the expression of E-cadherin, an O-GlcNAcylated protein in ovarian cancer cells, was reduced by OGA inhibition in OVCAR3 cells and elevated by OGT silencing in HO-8910PM cells. These results indicate that O-GlcNAcylation could enhance ovarian cancer cell migration and decrease the expression of E-cadherin. Our studies also suggest that O-GlcNAcylation might become another potential target for the therapy of ovarian cancer. (C) 2013 Elsevier Inc. All rights reserved.