The mucin-type glycosylating enzyme polypeptide N-acetylgalactosaminyltransferase 14 promotes the migration of ovarian cancer by modifying mucin 13
The mucin-type glycosylating enzyme polypeptide N-acetylgalactosaminyltransferase 14 promotes the migration of ovarian cancer by modifying mucin 13
复制标题
粘蛋白型糖基化酶多肽N-乙酰半乳糖氨基转移酶14通过修饰粘蛋白13促进卵巢癌迁移
DOI：
10.3892/or.2013.2493
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发表时间：
2013-08-01
期刊：
影响因子：
4.2
通讯作者：
Yang, Zhu
中科院分区：
文献类型：
--
作者：
Wang, Ranran;Yu, Chao;Yang, Zhu
o -糖基化蛋白的高表达是卵巢癌细胞与细胞迁移相关的显著特征之一，这可能与糖基转移酶的表达上调有关。因此，阐明糖基转移酶及其底物可以提高我们对其在肿瘤转移中的作用的理解。在本研究中，我们报道了用小干扰RNA敲低多肽n -乙酰半乳糖氨基转移酶14 （GALNT14）可显著抑制细胞迁移和改变细胞形态。免疫沉淀和western blot分析表明，GALNT14参与了跨膜粘蛋白13 （MUC13）的糖基化，卵巢癌细胞中MUC13的糖基化水平明显高于正常/良性卵巢组织。此外，调节上皮性卵巢癌（EOC）细胞迁移能力的白细胞介素-8 （IL-8）对GALNT14和肿瘤相关碳水化合物表位Tn抗原的表达无显著影响。此外，细胞外信号调节激酶1/2 （ERK1/2）抑制剂可调节GALNT14的表达水平。我们的发现提供了证据，GALNT14可能通过MUC13的异常糖基化而不是通过IL-8途径参与卵巢癌的发生。这些数据为了解MUC13在肿瘤转移中的功能提供了新的见解，并可能有助于开发新的EOC抗癌药物。
A high expression of O-glycosylated proteins is one of the prominent characteristics of ovarian carcinoma cells associated with cell migration, which would be attributed to the upregulated expression of glycosyltransferases. Therefore, elucidating glycosyltransferases and their substrates may improve our understanding of their roles in tumor metastasis. In the present study, we reported that knockdown of polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14) by small interfering RNA significantly suppressed the cell migration and altered cellular morphology. Immunoprecipitation and western blot analyses indicated that GALNT14 contributed to the glycosylation of transmembrane mucin 13 (MUC13), which was significantly higher in ovarian cancer cells compared with the normal/benign ovary tissues. Furthermore, interleukin-8 (IL-8), which could regulate the migration ability of epithelial ovarian cancer (EOC) cells, had no remarkable effect on the expression of GALNT14 and the tumor-associated carbohydrate epitope Tn antigen. In addition, extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor modulated the expression levels of GALNT14. Our findings provide evidence that GALNT14 may contribute to ovarian carcinogenesis through aberrant glycosylation of MUC13, but not through the IL-8 pathway. These data provide novel insights into understanding the function of MUC13 on neoplasm metastasis and may aid in the development of new anticancer drugs for EOC.