ArticleThe Journal of biological chemistry2016
Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the p53 Pathway in Ovarian Cancer Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 109 citations in OpenAlex.
- O-GlcNAcylation: the metabolic-immune translator in tumor evolution and treatment.Molecular medicine (Cambridge, Mass.) · 2026Review
- Glycosylation modification: a trigger for obesity and its complications?Molecular medicine (Cambridge, Mass.) · 2026Review
- ONX-0914 Suppresses Hormone-Sensitive Prostate Cancer by Promoting O-GlcNAcylation-Mediated Stabilization of TCF7L1.Oncology research · 2026Article
- O-GlcNAcylation of DDB1 at Ser-764 by OGT promotes cancer cell stemness in colorectal cancer through increased polyubiquitination of p53.Scientific reports · 2025Article
- Cell cycle regulation in cancer cells by O-GlcNAcylation.Glycoconjugate journal · 2025Review
- O-GlcNAcylation in ovarian tumorigenesis and its therapeutic implications.Translational oncology · 2025Review
- Phosphofructokinase-1 in Cancer: A Promising Target for Diagnosis and Therapy.Recent patents on anti-cancer drug discovery · 2025Review
- Dynamic O-GlcNAcylation coordinates etoposide-triggered tumor cell pyroptosis by regulating p53 stability.The Journal of biological chemistry · 2025Article
- A novel histone acetylation-associated gene signature with prognostic value in Ewing sarcoma.Discover oncology · 2024Article
- Regulation of AUF1 alternative splicing by hnRNPA1 and SRSF2 modulate the sensitivity of ovarian cancer cells to cisplatin.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Metabolic adaptations in prostate cancer.British journal of cancer · 2024Review
- Glycan diversity in ovarian cancer: Unraveling the immune interplay and therapeutic prospects.Seminars in immunopathology · 2024Review
- Metabolomic Analysis of Histological Composition Variability of High-Grade Serous Ovarian Cancer UsingInternational journal of molecular sciences · 2024Article
- OGA mutant aberrantly hydrolyzes O-GlcNAc modification from PDLIM7 to modulate p53 and cytoskeleton in promoting cancer cell malignancy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeted Protein O-GlcNAcylation Using Bifunctional Small Molecules.Journal of the American Chemical Society · 2024Article
- Reciprocal regulation of TWIST1 and OGT determines the decitabine efficacy in MDS/AML.Cell communication and signaling : CCS · 2023Article
- Regulation of Primary Cilium Length by O-GlcNAc during Neuronal Development in a Human Neuron Model.Cells · 2023Article
- Emerging field:Frontiers in molecular biosciences · 2023Review
- Recent development of analytical methods for disease-specific proteinRSC advances · 2022Review
- O-GlcNAcylation: an important post-translational modification and a potential therapeutic target for cancer therapy.Molecular medicine (Cambridge, Mass.) · 2022Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
O-GlcNAcylation is a dynamic post-translational modification consisting of the addition of a single N-acetylglucosamine sugar to serine and threonine residues in proteins by the enzyme O-linked β-N-acetylglucosamine transferase (OGT), whereas the enzyme O-GlcNAcase (OGA) removes the modification. In cancer, tumor samples present with altered O-GlcNAcylation; however, changes in O-GlcNAcylation are not consistent between tumor types. Interestingly, the tumor suppressor p53 is modified by O-GlcNAc, and most solid tumors contain mutations in p53 leading to the loss of p53 function. Because ovarian cancer has a high frequency of p53 mutation rates, we decided to investigate the relationship between O-GlcNAcylation and p53 function in ovarian cancer. We measured a significant decrease in O-GlcNAcylation of tumor tissue in an ovarian tumor microarray. Furthermore, O-GlcNAcylation was increased, and OGA protein and mRNA levels were decreased in ovarian tumor cell lines not expressing the protein p53. Treatment with the OGA inhibitor Thiamet-G (TMG), silencing of OGA, or overexpression of OGA and OGT led to p53 stabilization, increased nuclear localization, and increased protein and mRNA levels of p53 target genes. These data suggest that changes in O-GlcNAc homeostasis activate the p53 pathway. Combination treatment of the chemotherapeutic cisplatin with TMG decreased tumor cell growth and enhanced cell cycle arrest without impairing cytotoxicity. The effects of TMG on tumor cell growth were partially dependent on wild type p53 activation. In conclusion, changes in O-GlcNAc homeostasis activate the wild type p53 pathway in ovarian cancer cells, and OGA inhibition has the potential as an adjuvant treatment for ovarian carcinoma.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.