ArticleNature communications2017
Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed, 205 citations in OpenAlex.
- Computerized neurocognitive training for improving dietary health and facilitating weight loss.Journal of behavioral medicine · 2019Trial
- Glucose repression ofbioRxiv : the preprint server for biology · 2026Article
- The transcription factor C/EBPβ promotes hyperglycemia-elicited glycolysis and liver cancer progression.Nature communications · 2026Article
- Trehalose-6-phosphate synthase promotes thermotolerance by governing glycolytic flux inbioRxiv : the preprint server for biology · 2026Article
- Review
- Multilayered control of hexose uptake and phosphorylation through specialized sugar kinases in Nakaseomyces glabratus.Fungal biology and biotechnology · 2026Article
- Fructose-1,6-bisphosphate couples glycolytic activity to cell adhesion.Nature cell biology · 2026Article
- The return of metabolism: biochemistry and physiology of glycolysis.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Glycolysis-dependent sulfur metabolism orchestrates morphological plasticity and virulence in fungi.eLife · 2026Article
- Insulin-Dependence and Survival in Pancreatic Neuroendocrine Tumors: Results From the US-NTSG Group.Journal of surgical oncology · 2026Article
- PFKM governs metabolic shifts throughout skeletal muscle differentiation.Nature metabolism · 2026Article
- Functional requirements of the liver isoform of phosphofructokinase-1 in breast cancer cell migration.Journal of cell science · 2025Article
- Conserved function of a RasGEF-mediated pathway in the metabolic compensation of the circadian clock.The FEBS journal · 2025Article
- A noncanonical role of glycolytic metabolites controlling the timing of mouse embryo segmentation.Science advances · 2025Article
- Glucose metabolism and its direct action in cancer and immune regulation: opportunities and challenges for metabolic targeting.Journal of biomedical science · 2025Review
- Article
- Glycolytic flux controls retinal progenitor cell differentiation via regulating Wnt signaling.eLife · 2025Article
- The synthesis, degradation and biological function of trehalose- 6-phosphate.Stress biology · 2025Review
- PKA plays a conserved role in regulating gene expression and metabolic adaptation by phosphorylating Rpd3/HDAC1.Nature communications · 2025Article
- Small Extracellular Vesicle-Derived Nicotinamide Phosphoribosyltransferase (NAMPT) Induces Acyl-Coenzyme A Synthetase SLC27A4-Mediated Glycolysis to Promote Hepatocellular Carcinoma.Journal of extracellular vesicles · 2025Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Yeast and cancer cells share the unusual characteristic of favoring fermentation of sugar over respiration. We now reveal an evolutionary conserved mechanism linking fermentation to activation of Ras, a major regulator of cell proliferation in yeast and mammalian cells, and prime proto-oncogene product. A yeast mutant (tps1∆) with overactive influx of glucose into glycolysis and hyperaccumulation of Fru1,6bisP, shows hyperactivation of Ras, which causes its glucose growth defect by triggering apoptosis. Fru1,6bisP is a potent activator of Ras in permeabilized yeast cells, likely acting through Cdc25. As in yeast, glucose triggers activation of Ras and its downstream targets MEK and ERK in mammalian cells. Biolayer interferometry measurements show that physiological concentrations of Fru1,6bisP stimulate dissociation of the pure Sos1/H-Ras complex. Thermal shift assay confirms direct binding to Sos1, the mammalian ortholog of Cdc25. Our results suggest that the Warburg effect creates a vicious cycle through Fru1,6bisP activation of Ras, by which enhanced fermentation stimulates oncogenic potency.Yeast and cancer cells both favor sugar fermentation in aerobic conditions. Here the authors describe a conserved mechanism from yeast to mammals where the glycolysis intermediate fructose-1,6-bisphosphate binds Cdc25/Sos1 and couples increased glycolytic flux to increased Ras proto-oncoprotein activity.
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