ArticleCell reports2013
Suppression of nucleotide metabolism underlies the establishment and maintenance of oncogene-induced senescence.
Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
196 citing papers in PubMed, 290 citations in OpenAlex.
- Nucleotides as an Anti-Aging Supplementation in Older Adults: A Randomized Controlled Trial (TALENTs study).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Trial
- Tumor-associated B-cells induce tumor heterogeneity and therapy resistance.Nature communications · 2017Trial
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- ERCC6 at the Transcription-Replication Interface: Integration of Transcription-Coupled Repair with Replication Stress Responses.International journal of molecular sciences · 2026Review
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Molecular mechanisms and recent advances in cellular senescence.Cell & bioscience · 2026Review
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Fatty acid channelling into triglycerides and oxylipins drives ferroptosis resistance during oncogenic BRAF-induced senescence.Cell death and differentiation · 2026Article
- Metabolic crosstalk among cancer-associated fibroblasts, adipocytes and immune cells as an immunosuppressive tumor microenvironment driver.Experimental & molecular medicine · 2026Review
- p53 increases phospholipid headgroup scavenging in senescence.Nature cell biology · 2026Article
- AKG-TET axis is central to senescence plasticity.iScience · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- NSMF modulates replication stress to facilitate colorectal cancer progression.Nucleic acids research · 2026Article
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- AVN944 Elicits Apoptotic Responses and Impedes Tumorigenic Potential in Ewing's Sarcoma Cells.International journal of biological sciences · 2026Article
- Article
- Decoding nucleoside supplementation: how thymidine outperforms ribonucleosides in accelerating mammalian replication forks.Nucleic acids research · 2025Article
- Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress.Oncogene · 2025Article
- WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRASCell death & disease · 2025Article
136 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Oncogene-induced senescence is characterized by a stable cell growth arrest, thus providing a tumor suppression mechanism. However, the underlying mechanisms for this phenomenon remain unknown. Here, we show that a decrease in deoxyribonucleotide triphosphate (dNTP) levels underlies oncogene-induced stable senescence-associated cell growth arrest. The decrease in dNTP levels is caused by oncogene-induced repression of ribonucleotide reductase subunit M2 (RRM2), a rate-limiting protein in dNTP synthesis. This precedes the senescence-associated cell-cycle exit and coincides with the DNA damage response. Consistently, RRM2 downregulation is both necessary and sufficient for senescence. Strikingly, suppression of nucleotide metabolism by RRM2 repression is also necessary for maintenance of the stable senescence-associated cell growth arrest. Furthermore, RRM2 repression correlates with senescence status in benign nevi and melanoma, and its knockdown drives senescence of melanoma cells. These data reveal the molecular basis whereby the stable growth arrest of oncogene-induced senescence is established and maintained through suppression of nucleotide metabolism.
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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.