ArticleOncogene2022
Thymidylate synthase O-GlcNAcylation: a molecular mechanism of 5-FU sensitization in colorectal cancer.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- O-GlcNAcylation Regulation of SNAP29-Dependent Autophagy Activation Dictates Chemoresistance in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Decoding the Hexosamine Biosynthesis Pathway: Implications for Novel Therapeutic Strategies in Sarcoma.Journal of cellular physiology · 2026Review
- Everolimus destabilizes thymidylate synthase via suppressing its O-GlcNAcylation and sensitizes HER2-negative breast cancer to fluorouracil.Cell death & disease · 2026Article
- O-GlcNAcylation at the tumor-immune interface: a metabolic post-translational code driving immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- CF10 Displayed Improved Activity Relative to 5-FU in a Mouse CRLM Model Under Conditions of Physiological Folate.Cancers · 2025Article
- Immune cell metabolism in cancer drug resistance: Advances in target discovery and clinical translation.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Exploring biomarkers and molecular mechanisms of Type 2 diabetes mellitus promotes colorectal cancer progression based on transcriptomics.Scientific reports · 2025Article
- CF10/LV overcomes acquired resistance to 5-FU/LV in colorectal cancer cells through downregulation of the c-Myc/ABCB5 axis.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- The roles of OGT and its mechanisms in cancer.Cell & bioscience · 2024Review
- 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
- Recent progress and challenges of MOF-based nanocomposites in bioimaging, biosensing and biocarriers for drug delivery.Nanoscale advances · 2024Review
- Regulatory mechanisms of one-carbon metabolism enzymes.The Journal of biological chemistry · 2023Review
- Targeting USP8 Inhibits O-GlcNAcylation of SLC7A11 to Promote Ferroptosis of Hepatocellular Carcinoma via Stabilization of OGT.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Review
- ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting repair of DNA damage.Oncology reports · 2022Article
- TargetingFrontiers in oncology · 2022Review
- Genome-wide CRISPR Screening Reveals Pyrimidine Metabolic Reprogramming in 5-FU Chronochemotherapy of Colorectal Cancer.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alteration of O-GlcNAcylation, a dynamic posttranslational modification, is associated with tumorigenesis and tumor progression. Its role in chemotherapy response is poorly investigated. Standard treatment for colorectal cancer (CRC), 5-fluorouracil (5-FU), mainly targets Thymidylate Synthase (TS). TS O-GlcNAcylation was reported but not investigated yet. We hypothesize that O-GlcNAcylation interferes with 5-FU CRC sensitivity by regulating TS. In vivo, we observed that combined 5-FU with Thiamet-G (O-GlcNAcase (OGA) inhibitor) treatment had a synergistic inhibitory effect on grade and tumor progression. 5-FU decreased O-GlcNAcylation and, reciprocally, elevation of O-GlcNAcylation was associated with TS increase. In vitro in non-cancerous and cancerous colon cells, we showed that 5-FU impacts O-GlcNAcylation by decreasing O-GlcNAc Transferase (OGT) expression both at mRNA and protein levels. Reciprocally, OGT knockdown decreased 5-FU-induced cancer cell apoptosis by reducing TS protein level and activity. Mass spectrometry, mutagenesis and structural studies mapped O-GlcNAcylated sites on T251 and T306 residues and deciphered their role in TS proteasomal degradation. We reveal a crosstalk between O-GlcNAcylation and 5-FU metabolism in vitro and in vivo that converges to 5-FU CRC sensitization by stabilizing TS. Overall, our data propose that combining 5-FU-based chemotherapy with Thiamet-G could be a new way to enhance CRC response to 5-FU.
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Registered trials
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.