ArticleMolecular cancer research : MCR2020
Inhibition of O-GlcNAc Transferase Renders Prostate Cancer Cells Dependent on CDK9.
Article in Molecular cancer research : MCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Decoding the Hexosamine Biosynthesis Pathway: Implications for Novel Therapeutic Strategies in Sarcoma.Journal of cellular physiology · 2026Review
- Small molecule splicing modulators that disrupt O-GlcNAc homeostasis.Nature communications · 2026Article
- O‑GlcNAcylation as an emerging molecular target for cholangiocarcinoma therapy (Review).Oncology reports · 2025Review
- Harnessing organoid technology in urological cancer: advances and applications in urinary system tumors.World journal of surgical oncology · 2025Review
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- Dynamic O-GlcNAcylation and phosphorylation attract and expel proteins from RNA polymerase II to regulate mRNA maturation.Journal of biomedical science · 2025Article
- O-GlcNAc-modified HOXA9 suppresses ferroptosis via promoting UBR5-mediated SIRT6 degradation in nasopharyngeal carcinoma.Neoplasia (New York, N.Y.) · 2025Article
- Dynamic O-GlcNAcylation coordinates etoposide-triggered tumor cell pyroptosis by regulating p53 stability.The Journal of biological chemistry · 2025Article
- Compromised CDK12 activity causes dependency on the high activity of O-GlcNAc transferase.Glycobiology · 2024Article
- O-GlcNAcylation inhibition redirects the response of colon cancer cells to chemotherapy from senescence to apoptosis.Cell death & disease · 2024Article
- Emerging frontiers in androgen receptor research for prostate Cancer: insights from the 2nd international androgen receptor Symposium.Journal of experimental & clinical cancer research : CR · 2024Article
- Let's Go 3D! New Generation of Models for Evaluating Drug Response and Resistance in Prostate Cancer.International journal of molecular sciences · 2023Review
- Revealing the History and Mystery of RNA-Seq.Current issues in molecular biology · 2023Review
- O-GlcNAc transferase maintains metabolic homeostasis in response to CDK9 inhibition.Glycobiology · 2022Article
- O-GlcNAc transferase couples MRE11 to transcriptionally active chromatin to suppress DNA damage.Journal of biomedical science · 2022Article
- O-GlcNAcylation regulation of cellular signaling in cancer.Cellular signalling · 2022Review
- Inhibition of O-GlcNAc transferase sensitizes prostate cancer cells to docetaxel.Frontiers in oncology · 2022Article
- How Nanotechniques Could Vitalize the O-GlcNAcylation-Targeting Approach for Cancer Therapy.International journal of nanomedicine · 2022Review
- Ogt Demonstrated Conspicuous Clinical Significance in Cancers, from Pan-Cancer to Small-Cell Lung Cancer.Journal of oncology · 2022Article
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
O-GlcNAc transferase (OGT) is a nutrient-sensitive glycosyltransferase that is overexpressed in prostate cancer, the most common cancer in males. We recently developed a specific and potent inhibitor targeting this enzyme, and here, we report a synthetic lethality screen using this compound. Our screen identified pan-cyclin-dependent kinase (CDK) inhibitor AT7519 as lethal in combination with OGT inhibition. Follow-up chemical and genetic approaches identified CDK9 as the major target for synthetic lethality with OGT inhibition in prostate cancer cells. OGT expression is regulated through retention of the fourth intron in the gene and CDK9 inhibition blunted this regulatory mechanism. CDK9 phosphorylates carboxy-terminal domain (CTD) of RNA Polymerase II to promote transcription elongation. We show that OGT inhibition augments effects of CDK9 inhibitors on CTD phosphorylation and general transcription. Finally, the combined inhibition of both OGT and CDK9 blocked growth of organoids derived from patients with metastatic prostate cancer, but had minimal effects on normal prostate spheroids. We report a novel synthetic lethal interaction between inhibitors of OGT and CDK9 that specifically kills prostate cancer cells, but not normal cells. Our study highlights the potential of combining OGT inhibitors with other treatments to exploit cancer-specific vulnerabilities. IMPLICATIONS: The primary contribution of OGT to cell proliferation is unknown, and in this study, we used a compound screen to indicate that OGT and CDK9 collaborate to sustain a cancer cell-specific pro-proliferative program. A better understanding of how OGT and CDK9 cross-talk will refine our understanding of this novel synthetic lethal interaction.
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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.