ArticleCell metabolism2023
Regulation of VKORC1L1 is critical for p53-mediated tumor suppression through vitamin K metabolism.
Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Calciphylaxis in chronic kidney disease: a systematic review of pathomechanisms and risk factors for calcific uremic arteriolopathy.Renal failure · 2026Pooled it
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Prognostic value of genes associated with metastasis and propionate metabolism in rectal cancer.Journal of gastrointestinal oncology · 2026Article
- Menaquinone-4 protects CD8Science China. Life sciences · 2026Article
- Skeletal muscle-specific deficiency of Rab geranylgeranyl transferase beta subunit induces myopathy and exacerbates the symptoms caused by HMG-CoA reductase deficiency in mice.Molecular metabolism · 2026Article
- Ferroptosis as an approach to leverage cancer metabolism.Trends in cell biology · 2026Review
- VKORC1L1-mediated vitamin K recycling counters ferroptosis to promote endothelial repair.Scientific reports · 2026Article
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Ferroptosis in Neuropsychiatric and Neurodegenerative Disorders: Shared Mechanisms and Disease-Specific Signatures.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A GPX1-OSBPL8 axis mediates noncanonical in vivo ferroptosis and cancer growth suppression.Cell · 2026Article
- LINC-AC092535.5 regulates MICAL2 mRNA level to inhibit p53-mediated ferroptosis in nasopharyngeal carcinoma.Oncogene · 2026Article
- Ferroptotic neurodegeneration and diet: a narrative review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Dissecting Complex Interactions Between Ferroptosis and the Proteasome.bioRxiv : the preprint server for biology · 2026Article
- Lipocalin 2 orchestrates resistance to ferroptosis via AXL.Cell reports · 2026Article
- Liproxstatin-1 Attenuates Retinal Ischemia-Reperfusion Injury by Suppressing EGR1-Mediated Ferroptosis.Antioxidants (Basel, Switzerland) · 2026Article
- Repurposing dronedarone induces ferroptosis through GPX4 inactivation and degradation in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Lipids grease the chain of cancer progression.Trends in cancer · 2026Review
- Vitamin B2 metabolism promotes FSP1 stability to prevent ferroptosis.Nature structural & molecular biology · 2026Article
- VKORC1L1 Downregulation Induced Vitamin K Cycle Disorder Exacerbates Neuronal Ferroptosis After Spinal Cord Injury.Molecular neurobiology · 2026Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Here, we identified vitamin K epoxide reductase complex subunit 1 like 1 (VKORC1L1) as a potent ferroptosis repressor. VKORC1L1 protects cells from ferroptosis by generating the reduced form of vitamin K, a potent radical-trapping antioxidant, to counteract phospholipid peroxides independent of the canonical GSH/GPX4 mechanism. Notably, we found that VKORC1L1 is also a direct transcriptional target of p53. Activation of p53 induces downregulation of VKORC1L1 expression, thus sensitizing cells to ferroptosis for tumor suppression. Interestingly, a small molecular inhibitor of VKORC1L1, warfarin, is widely prescribed as an FDA-approved anticoagulant drug. Moreover, warfarin represses tumor growth by promoting ferroptosis in both immunodeficient and immunocompetent mouse models. Thus, by downregulating VKORC1L1, p53 executes the tumor suppression function by activating an important ferroptosis pathway involved in vitamin K metabolism. Our study also reveals that warfarin is a potential repurposing drug in cancer therapy, particularly for tumors with high levels of VKORC1L1 expression.
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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.