ArticleOncotarget2017
Vitamin K epoxide reductase regulation of androgen receptor activity.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Risk of osteoporosis in patients treated with direct oral anticoagulants vs. warfarin: an analysis of observational studies.Frontiers in endocrinology · 2023Pooled it
- Pharmacogenetic determinants of outcomes on triplet hepatic artery infusion and intravenous cetuximab for liver metastases from colorectal cancer (European trial OPTILIV, NCT00852228).British journal of cancer · 2017Trial
- Effects of Docosahexaenoic Acid on Prostate Cancer.Journal of xenobiotics · 2025Review
- Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to Therapeutic Innovation.International journal of molecular sciences · 2025Review
- Association between vitamin intake and prostate cancer: a cross-sectional study.Frontiers in nutrition · 2025Article
- Sarcopenia in chronic kidney disease: from bench to bedside.The Korean journal of internal medicine · 2023Review
- The role of PPARγ in prostate cancer development and progression.British journal of cancer · 2023Review
- Molecular Modeling of Allosteric Site of Isoform-Specific Inhibition of the Peroxisome Proliferator-Activated Receptor PPARγ.Biomolecules · 2022Article
- Histone methyltransferase KMT2D mediated lipid metabolism via peroxisome proliferator-activated receptor gamma in prostate cancer.Translational cancer research · 2022Article
- Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements.Frontiers in toxicology · 2022Article
- Identification of an irreversible PPARγ antagonist with potent anticancer activity.Pharmacology research & perspectives · 2020Review
- Peroxisome proliferator-activated receptor gamma controls prostate cancer cell growth through AR-dependent and independent mechanisms.The Prostate · 2020Article
- MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.Bioscience trends · 2019Article
- Review
- Multiple Modes of Vitamin K Actions in Aging-Related Musculoskeletal Disorders.International journal of molecular sciences · 2019Review
- Molecules targeting the androgen receptor (AR) signaling axis beyond the AR-Ligand binding domain.Medicinal research reviews · 2019Review
- Androgen Receptor Dependence.Advances in experimental medicine and biology · 2019Review
- Different roles of peroxisome proliferator-activated receptor gamma isoforms in prostate cancer.American journal of clinical and experimental urology · 2019Article
- A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor.Nature chemical biology · 2017Article
- Crosstalk between the Androgen Receptor and PPAR Gamma Signaling Pathways in the Prostate.PPAR research · 2017Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Long-term use of warfarin has been shown to be associated with a reduced risk of prostate cancer. Warfarin belongs to the vitamin K antagonist class of anticoagulants, which inhibit vitamin K epoxide reductase (VKOR). The vitamin K cycle is primarily known for its role in γ-carboxylation, a rare post-translational modification important in blood coagulation. Here we show that warfarin inhibits the transcriptional activity of the androgen receptor (AR), an important driver of prostate cancer development and progression. Warfarin treatment or knockdown of its target VKOR inhibits the activity of AR both in cell lines and in mouse prostate tissue. We demonstrate that AR can be γ-carboxylated, and mapped the γ-carboxylation to glutamate residue 2 (E2) using mass spectrometry. However, mutation of E2 and other glutamates on AR failed to suppress the effects of warfarin on AR suggesting that inhibition of AR is γ-carboxylation independent. To identify pathways upstream of AR signaling that are affected by warfarin, we performed RNA-seq on prostates of warfarin-treated mice. We found that warfarin inhibited peroxisome proliferator-activated receptor gamma (PPARγ) signaling, which in turn, inhibited AR signaling. Although warfarin is unfit for use as a chemopreventative due to its anticoagulatory effects, our data suggest that its ability to reduce prostate cancer risk is independent of its anticoagulation properties. Furthermore, our data show that warfarin inhibits PPARγ and AR signaling, which suggests that inhibition of these pathways could be used to reduce the risk of developing prostate cancer.
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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.