O-GlcNAcylation promotes migration and invasion in human ovarian cancer cells via the RhoA/ROCK/MLC pathway

التفاصيل البيبلوغرافية
العنوان: O-GlcNAcylation promotes migration and invasion in human ovarian cancer cells via the RhoA/ROCK/MLC pathway
المؤلفون: Xiaofei Shi, Jingyun Wang, Yichao Niu, Ye Xia
المصدر: Molecular Medicine Reports
بيانات النشر: D.A. Spandidos, 2017.
سنة النشر: 2017
مصطلحات موضوعية: 0301 basic medicine, Cancer Research, RHOA, Myosin light-chain kinase, Myosin Light Chains, Carcinoma, Ovarian Epithelial, migration, N-Acetylglucosaminyltransferases, Biochemistry, Acetylglucosamine, 03 medical and health sciences, O-GlcNAcylation, RNA interference, Cell Movement, Cell Line, Tumor, Genetics, Gene silencing, Humans, Neoplasm Invasiveness, Neoplasms, Glandular and Epithelial, Protein kinase A, Molecular Biology, Ovarian Neoplasms, rho-Associated Kinases, RhoA/ROCK/MLC, biology, Oncogene, Ovary, Articles, invasion, Cell biology, 030104 developmental biology, ovarian cancer, Oncology, biology.protein, Molecular Medicine, Phosphorylation, Female, Signal transduction, rhoA GTP-Binding Protein, Signal Transduction
الوصف: O-GlcNAcylation is a dynamic and reversible post-translational modification associated with the regulation of multiple cellular functions. The addition and removal of O-Linked β-N-acetylglucosamine (O-GlcNAc) on target proteins is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. Accumulating evidence suggests that O-GlcNAcylation is associated with the malignancy of several types of human cancer. To investigate the effect of O-GlcNAcylation on ovarian cancer phenotypes, global O-GlcNAc levels were decreased by OGT silencing through RNA interference and increased by inhibiting OGA activity with Thiamet-G. Transwell assay results demonstrated that OGT silencing inhibited the migration and invasion of SKOV3 and 59M ovarian cells in vitro, while Thiamet-G treatment promoted migration and invasion. Furthermore, a pull-down assay and western blot analysis demonstrated that Thiamet-G treatment enhanced RhoA activity and the phosphorylation of the Rho-associated protein kinase (ROCK) substrate, myosin light chain (MLC), while OGT silencing attenuated RhoA activity and MLC phosphorylation. In addition, RhoA silencing via RNA interference and inhibition of ROCK activity with Y-27632 prevented Thiamet-G-induced increases in cell migration and invasion. These data suggest that O-GlcNAcylation augments the motility of ovarian cancer cells via the RhoA/ROCK/MLC signaling pathway. Therefore, O-GlcNAcylation may be a potential target for the diagnosis and treatment of ovarian cancer.
اللغة: English
تدمد: 1791-3004
1791-2997
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8843c16f3f5a9635ac6592396aee5d85
http://europepmc.org/articles/PMC5364967
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....8843c16f3f5a9635ac6592396aee5d85
قاعدة البيانات: OpenAIRE