ArticleThe EMBO journal2017
Regulation of hypoxia responses by flavin adenine dinucleotide-dependent modulation of HIF-1α protein stability.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Multi-omic cell free DNA profiles of cerebral spinal fluid from lung cancer metastasis to the brain.NAR cancer · 2026Article
- Proteasome-Enriched hPPSCs-Derived EVs Attenuate Hypoxic Injury in Endothelial Cells via Proteasome-Mediated HIF-1α Degradation.International journal of molecular sciences · 2026Article
- Review
- Hypoxia Induces Immunosuppression by Silencing STING in Cancer.Cancer research · 2025Article
- In Silico Identification of LSD1 Inhibition-Responsive Targets in Small Cell Lung Cancer.Bioengineering (Basel, Switzerland) · 2025Article
- Dietary riboflavin (vitamin B2) intake and osteoporosis in U.S. female adults: unveiling of association and exploration of potential molecular mechanisms.Nutrition journal · 2025Article
- GPX3 Overexpression Ameliorates Cardiac Injury Post Myocardial Infarction Through Activating LSD1/Hif1α Axis.Journal of cellular and molecular medicine · 2025Article
- Dual targeting of KDM1A and antioxidants is an effective anticancer strategy.bioRxiv : the preprint server for biology · 2024Article
- Review
- Role of NADCellular and molecular neurobiology · 2023Review
- Gut microbiome signatures of extreme environment adaption in Tibetan pig.NPJ biofilms and microbiomes · 2023Article
- Quantum based effects of therapeutic nuclear magnetic resonance persistently reduce glycolysis.iScience · 2022Article
- Breath of Fresh Air: Toward Unraveling the Molecular Underpinnings of Sleep Apnea.American journal of respiratory and critical care medicine · 2022Article
- Targeting lysine-specific demethylase 1A inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Article
- Mechanisms of carcinogenic activity triggered by lysine-specific demethylase 1A.Frontiers in pharmacology · 2022Review
- Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases.Journal of biomedical science · 2021Review
- PCAT-1 facilitates breast cancer progression via binding to RACK1 and enhancing oxygen-independent stability of HIF-1α.Molecular therapy. Nucleic acids · 2021Article
- Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types-Tumour Microenvironment and Metabolism.International journal of molecular sciences · 2020Review
- Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation.Journal of experimental & clinical cancer research : CR · 2020Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxygen deprivation induces a range of cellular adaptive responses that enable to drive cancer progression. Here, we report that lysine-specific demethylase 1 (LSD1) upregulates hypoxia responses by demethylating RACK1 protein, a component of hypoxia-inducible factor (HIF) ubiquitination machinery, and consequently suppressing the oxygen-independent degradation of HIF-1α. This ability of LSD1 is attenuated during prolonged hypoxia, with a decrease in the cellular level of flavin adenine dinucleotide (FAD), a metabolic cofactor of LSD1, causing HIF-1α downregulation in later stages of hypoxia. Exogenously provided FAD restores HIF-1α stability, indicating a rate-limiting role for FAD in LSD1-mediated HIF-1α regulation. Transcriptomic analyses of patient tissues show that the HIF-1 signature is highly correlated with the expression of LSD1 target genes as well as the enzymes of FAD biosynthetic pathway in triple-negative breast cancers, reflecting the significance of FAD-dependent LSD1 activity in cancer progression. Together, our findings provide a new insight into HIF-mediated hypoxia response regulation by coupling the FAD dependence of LSD1 activity to the regulation of HIF-1α stability.
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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.