ArticleEMBO molecular medicine2022
Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 64 citations in OpenAlex.
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Lactate as a Master Regulator of Immune Suppression: From Metabolic Waste to Epigenetic Checkpoint in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Article
- Lactate-Primed NETosis Modulates Hepatic Regeneration During Acute Liver Failure via the TLR9/KLF15/AJUBA Axis.Cell proliferation · 2026Article
- Mitochondrial dysfunction and senescence accompany glioblastoma cell death triggered by a putative metabolic inhibitor.European journal of pharmacology · 2026Article
- RILPL2 suppresses metabolic reprogramming and progression of cervical cancer by attenuating LDHA protein stability and inhibiting H3K18 lactylation.Cell death & disease · 2026Article
- Lactate metabolism links reactive microglia, amyloid pathology, and Aβ dynamics.Journal of neuroinflammation · 2026Article
- Suppression of Tumor Aggression Through Metabolic Reprogramming via Oxamate Targeting LDHA.International journal of molecular sciences · 2026Review
- Stem cell functionbioRxiv : the preprint server for biology · 2026Article
- Pro-tumoral CaScientific reports · 2026Article
- Absolute dynamic and relative static: the relationship of glycolysis and OXPHOS in cancer development.Cell death discovery · 2026Review
- The antiseizure medication stiripentol inhibits mitochondrial complex I by blocking early-stage electron transfer.The Journal of biological chemistry · 2026Article
- Targeting Metabolic Vulnerabilities in Glioblastoma: a Framework for Multi-node Combination Therapy.Current oncology reports · 2026Review
- Beyond a metabolite: lactate and lactylation in lung diseases.Respiratory research · 2026Review
- C3G Downregulation Enhances Stemness in Glioblastoma Cells by Promoting PKM2 Upregulation.International journal of biological sciences · 2026Article
- LDAR is superior to other albumin-derived indices in predicting 28-day ICU mortality in critically ill patients with intracerebral hemorrhage: a two-cohort study.Frontiers in nutrition · 2026Article
- Metabolic interactions in the brain: the crucial roles of neurons, astrocytes, and microglia in health and disease.Frontiers in neuroscience · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Early metabolic reprogramming and carbonic anhydrase IX-mediated extracellular acidification drive radiotherapy-induced glioblastoma cell dedifferentiation.Acta neuropathologica communications · 2025Article
- The glioma microenvironment and its impact on antitumor immunity.Neuro-oncology advances · 2025Review
Corrections and comments
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Authors and funding
32 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lactate is a central metabolite in brain physiology but also contributes to tumor development. Glioblastoma (GB) is the most common and malignant primary brain tumor in adults, recognized by angiogenic and invasive growth, in addition to its altered metabolism. We show herein that lactate fuels GB anaplerosis by replenishing the tricarboxylic acid (TCA) cycle in absence of glucose. Lactate dehydrogenases (LDHA and LDHB), which we found spatially expressed in GB tissues, catalyze the interconversion of pyruvate and lactate. However, ablation of both LDH isoforms, but not only one, led to a reduction in tumor growth and an increase in mouse survival. Comparative transcriptomics and metabolomics revealed metabolic rewiring involving high oxidative phosphorylation (OXPHOS) in the LDHA/B KO group which sensitized tumors to cranial irradiation, thus improving mouse survival. When mice were treated with the antiepileptic drug stiripentol, which targets LDH activity, tumor growth decreased. Our findings unveil the complex metabolic network in which both LDHA and LDHB are integrated and show that the combined inhibition of LDHA and LDHB strongly sensitizes GB to therapy.
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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.