ArticleNature2017
The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 202 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
202 citing papers in PubMed, 350 citations in OpenAlex.
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Eprenetapopt in combination with Palbociclib exerts synthetic lethality in mantle cell lymphoma.Translational oncology · 2026Article
- Targeting PFKFB3 to enhance CDK4/6 inhibitor response in ER+ breast cancer.Breast cancer research : BCR · 2026Article
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- NKX2-1 regulates cell survival, maturation, and DNAdamage responses as a cofactor of RUNX1 in T-cell acute lymphoblastic leukemia.Haematologica · 2026Article
- ATM promotes PFKP nuclear translocation to balance glycolysis and homologous recombination repair.Nucleic acids research · 2026Article
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- GSK3i combinatorial treatments affect CDK4/6 and compensatory pathways in 3D preclinical models of pancreatic neuroendocrine tumors.Biology open · 2026Article
- Article
- Targeting PFKFB3 to enhance CDK4/6 inhibitor response in ER+ breast cancer.Research square · 2026Article
- MiR-181a-5p/CDK6 axis attenuates cell proliferation, migration and glycolytic reprogramming in oral squamous cell carcinoma.Cancer cell international · 2026Article
- Cysteine Metabolism in the Control of Oxidative Stress in Cancer, Focusing on Carbon and Sulfur Metabolism.Advances in experimental medicine and biology · 2026Review
- The Interdependence of Carbon Substrates and Metabolic Pathways Enables the Metabolic Plasticity of Cancer Cells.Advances in experimental medicine and biology · 2026Review
- BET Bromodomain Inhibition Reverses CDK4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer via Induction of miR-34a-5p.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Unveiling oncogene-induced senescence: a new frontier in prostate cancer prognosis and therapy.Discover oncology · 2025Article
- Article
- Review
- F-box protein FBXO32 ubiquitinates and stabilizes D-type cyclins to drive cancer progression.Nature communications · 2025Article
- Review
- Review
142 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
D-type cyclins (D1, D2 and D3) and their associated cyclin-dependent kinases (CDK4 and CDK6) are components of the core cell cycle machinery that drives cell proliferation. Inhibitors of CDK4 and CDK6 are currently being tested in clinical trials for patients with several cancer types, with promising results. Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2. This re-directs the glycolytic intermediates into the pentose phosphate (PPP) and serine pathways. Inhibition of cyclin D3-CDK6 in tumour cells reduces flow through the PPP and serine pathways, thereby depleting the antioxidants NADPH and glutathione. This, in turn, increases the levels of reactive oxygen species and causes apoptosis of tumour cells. The pro-survival function of cyclin D-associated kinase operates in tumours expressing high levels of cyclin D3-CDK6 complexes. We propose that measuring the levels of cyclin D3-CDK6 in human cancers might help to identify tumour subsets that undergo cell death and tumour regression upon inhibition of CDK4 and CDK6. Cyclin D3-CDK6, through its ability to link cell cycle and cell metabolism, represents a particularly powerful oncoprotein that affects cancer cells at several levels, and this property can be exploited for anti-cancer therapy.
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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.