ArticleNature structural & molecular biology2021
The tumor suppressor folliculin inhibits lactate dehydrogenase A and regulates the Warburg effect.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- LDH isozymes as targets for cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Engineering ZCIF@GSK Nanoplatform to Overcome Tumor Metabolism: LDHA Inhibition-Mediated Cuproptosis for Highly Efficient Oncotherapy.Advanced healthcare materials · 2026Article
- Intensification versus combination: revisiting the past and envisioning the future of LDHA inhibitors.Cancer chemotherapy and pharmacology · 2026Review
- Metaproteomic profiling reveals viral proteins and associated host proteomic alterations in glioblastoma.Scientific reports · 2026Article
- AFP confers the resistance of lenvatinib in hepatocellular carcinoma by activating PI3K/AKT/LDHA signaling axis.Discover oncology · 2026Article
- 5'tRF-GlyGCC Promotes Breast Cancer Progression via LDHA-Mediated Glycolysis and Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Decoding protein dynamics with limited proteolysis coupled to mass spectrometry: A comprehensive review.Journal of pharmaceutical analysis · 2025Review
- Ex vivo qualitative and quantitative analysis of fluorescently-labeled Hsp90 drug in human tumors.Cell stress & chaperones · 2025Article
- Construction and validation of a cell-in-cell related prognostic signature for hepatocellular carcinoma.Discover oncology · 2025Article
- Article
- Review
- First transcriptomic insight into the working muscles of racing pigeons during a competition flight.Molecular biology reports · 2024Article
- Proteomics Analysis of Pregnancy in Ewes under Heat Stress Conditions and Melatonin Administration.Animals : an open access journal from MDPI · 2024Article
- Colon adenocarcinoma and Birt-Hogg-Dubé syndrome in a young patient: case report and exploration of pathologic implications.Cancer biology & therapy · 2023Article
- Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery.Cell reports · 2023Article
- [NKD1 promotes glucose uptake in colon cancer cells by activating YWHAE transcription].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Functional TFEB activation characterizes multiple models of renal cystic disease and loss of polycystin-1.American journal of physiology. Renal physiology · 2023Article
- Glycolysis-related lncRNA TMEM105 upregulates LDHA to facilitate breast cancer liver metastasis via sponging miR-1208.Cell death & disease · 2023Article
- circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis.Open medicine (Warsaw, Poland) · 2023Article
- Influenced tumor microenvironment and tumor immunity by amino acids.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
Abstract
Aerobic glycolysis in cancer cells, also known as the 'Warburg effect', is driven by hyperactivity of lactate dehydrogenase A (LDHA). LDHA is thought to be a substrate-regulated enzyme, but it is unclear whether a dedicated intracellular protein also regulates its activity. Here, we identify the human tumor suppressor folliculin (FLCN) as a binding partner and uncompetitive inhibitor of LDHA. A flexible loop within the amino terminus of FLCN controls movement of the LDHA active-site loop, tightly regulating its enzyme activity and, consequently, metabolic homeostasis in normal cells. Cancer cells that experience the Warburg effect show FLCN dissociation from LDHA. Treatment of these cells with a decapeptide derived from the FLCN loop region causes cell death. Our data suggest that the glycolytic shift of cancer cells is the result of FLCN inactivation or dissociation from LDHA. Together, FLCN-mediated inhibition of LDHA provides a new paradigm for the regulation of glycolysis.
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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.