ArticleCell reports2016
KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 95 citations in OpenAlex.
- Dual activation of cuproptosis and excessive autophagy by copper-bismuth metal-organic frameworks-loaded detachable microneedles in oral leukoplakia.Materials today. Bio · 2026Article
- Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).Cell communication and signaling : CCS · 2026Review
- Succinate dehydrogenase-deficient cancer cells have increased susceptibility to Ym155-induced DNA damage.Endocrine-related cancer · 2026Article
- KDM4A promotes NEPC progression through regulation of MYC expression.Cancer letters · 2026Article
- Druggable target ATAD2 enhances the malignant progression and cooperates with E2F1 to up-regulate PDK1 expression in glioma.Genes & diseases · 2026Article
- Anti-tumor activity of CDYL2b in prostate cancer.Cancer letters · 2025Article
- RB1 controls differentiation through positive regulation of phosphoglycerate mutases.Cell death & disease · 2025Article
- Lycorine hydrochloride interferes with energy metabolism to inhibit chemoresistant glioblastoma multiforme cell growth through suppressing PDK3.Molecular and cellular biochemistry · 2025Article
- Therapeutic potential of microglial SMEK1 in regulating H3K9 lactylation in cerebral ischemia-reperfusion.Communications biology · 2024Article
- Exploring PDK3 inhibition in lung cancer through drug repurposing for potential therapeutic interventions.Scientific reports · 2024Article
- Pan-cancer analysis reveals PDK family as potential indicators related to prognosis and immune infiltration.Scientific reports · 2024Article
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- SET7/9-mediated methylation affects oncogenic functions of histone demethylase JMJD2A.JCI insight · 2023Article
- Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1.Cell death & disease · 2023Article
- Promotive role of eukaryotic translation initiation factor 4A isoform 3 in ovarian cancer cell growth and aerobic glycolysis through the pyruvate dehydrogenase kinase 4 signaling.The Kaohsiung journal of medical sciences · 2023Article
- Andrographolide suppresses aerobic glycolysis and induces apoptotic cell death by inhibiting pyruvate dehydrogenase kinase 1 expression.Oncology reports · 2023Article
- Article
- Recovering false negatives in CRISPR fitness screens with JLOE.Nucleic acids research · 2023Article
- KDM4 Demethylases: Structure, Function, and Inhibitors.Advances in experimental medicine and biology · 2023Article
- Epigenetic (De)regulation in Prostate Cancer.Cancer treatment and research · 2023Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The histone lysine demethylase KDM4A/JMJD2A has been implicated in prostate carcinogenesis through its role in transcriptional regulation. Here, we describe KDM4A as a E2F1 coactivator and demonstrate a functional role for the E2F1-KDM4A complex in the control of tumor metabolism. KDM4A associates with E2F1 on target gene promoters and enhances E2F1 chromatin binding and transcriptional activity, thereby modulating the transcriptional profile essential for cancer cell proliferation and survival. The pyruvate dehydrogenase kinases (PDKs) PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation. Downregulation of KDM4A leads to elevated activity of pyruvate dehydrogenase and mitochondrial oxidation, resulting in excessive accumulation of reactive oxygen species. The altered metabolic phenotypes can be partially rescued by ectopic expression of PDK1 and PDK3, indicating a KDM4A-dependent tumor metabolic regulation via PDK. Our results suggest that KDM4A is a key regulator of tumor metabolism and a potential therapeutic target for prostate cancer.
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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.