ArticleCell cycle (Georgetown, Tex.)2016
Lactate promotes glutamine uptake and metabolism in oxidative cancer cells.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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Who cites it
138 citing papers in PubMed, 215 citations in OpenAlex.
- Review
- Interplay between N6-methyladenosine RNA methylation and protein lactylation: a novel crosstalk linking metabolism and epigenetic regulation in human diseases.Journal of translational medicine · 2026Review
- Loss of MCT1 mediated lactate uptake causes delayed endplate maturation and intervertebral disc degeneration.Cell death & disease · 2026Article
- Article
- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- Lactate and lactylation: metabolic architects of tumor progression and metastasis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Pathogenic Mechanisms in Cervical Cancer: Energy Metabolism, Hypoxia and Therapy.Life (Basel, Switzerland) · 2026Review
- Blocking glutamine transport normalizes lymphatic vessels in hypoxic environments by attenuating glycolysis.bioRxiv : the preprint server for biology · 2026Article
- Lactate-lactylation in tumor angiogenesis and progression: mechanisms, biomarker potential, and therapeutic implications.Biomarker research · 2026Review
- mFrontiers in cell and developmental biology · 2026Review
- Glucose and Lactate, Starters or Intermediates of Cancer Metabolic Rewiring.Advances in experimental medicine and biology · 2026Review
- PCK2-Mediated PQBP1 Lactylation Promotes Asthmatic Inflammation through PRMT5 Inhibition.Research (Washington, D.C.) · 2026Article
- Review
- Lactate at the crossroads of tumor metabolism and immune escape: a new frontier in cancer therapy.Journal of translational medicine · 2025Review
- Untargeted Metabolomic Identifies Potential Seasonal Biomarkers of Semen Quality in Duroc Boars.Biology · 2025Article
- Long noncoding RNAs regulating enzymatic reactions in cancer.Experimental & molecular medicine · 2025Review
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
- Identification of molecular clusters and a risk prognosis model for diffuse large B-cell lymphoma based on lactate metabolism-related genes.Annals of hematology · 2025Article
- Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.Journal of advanced research · 2025Review
78 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling.
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