ArticleCancer & metabolism2021
GLUT5 (SLC2A5) enables fructose-mediated proliferation independent of ketohexokinase.
Article in Cancer & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Fructose 1-phosphate inhibits mannose phosphate isomerase to suppress hepatocellular carcinogenesis.Signal transduction and targeted therapy · 2026Article
- Unraveling the αVβ5-GLUT5 axis in breast cancer: linking extracellular matrix signaling to fructose metabolism: a scoping review.Molecular biology reports · 2026Article
- Trump, Coca-Cola and the fructose frenzy that influences brain and neuronal tumor development.Cell death and differentiation · 2026Article
- Testosterone deficiency synergistically exacerbates fructose-induced hepatic steatosis through gut microbiota and pyruvate in mice.American journal of physiology. Endocrinology and metabolism · 2026Article
- Epigenetic and metabolic rewiring in metastatic pheochromocytomas and paragangliomas driven by SDHB mutations.Communications biology · 2026Article
- Metabolic pathways fueling human spermatozoa capacitation and hyperactivation: a roadmap for spermatozoa bioenergetics.Frontiers in endocrinology · 2026Review
- Fructose metabolism as an adaptive survival axis in pancreatic cancer: mechanistic insights and therapeutic implications.Frontiers in medicine · 2026Review
- GLUT5 armouring enhances adoptive T-cell therapy anti-tumour activity under glucose-limiting conditions.Immunotherapy advances · 2025Article
- Fructose Metabolism in Cancer: Molecular Mechanisms and Therapeutic Implications.International journal of medical sciences · 2025Review
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- Biological role of fructose in the male reproductive system: Potential implications for prostate cancer.The Prostate · 2024Review
- The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- GLUT5: structure, functions, diseases and potential applications.Acta biochimica et biophysica Sinica · 2023Review
- PFKFB3 Inhibits Fructose Metabolism in Pulmonary Microvascular Endothelial Cells.American journal of respiratory cell and molecular biology · 2023Article
- Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD.Metabolism: clinical and experimental · 2023Article
- Establishing mammalian GLUT kinetics and lipid composition influences in a reconstituted-liposome system.Nature communications · 2023Article
- Fructose Induced KHK-C Increases ER Stress and Modulates Hepatic Transcriptome to Drive Liver Disease in Diet-Induced and Genetic Models of NAFLD.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundFructose is an abundant source of carbon and energy for cells to use for metabolism, but only certain cell types use fructose to proliferate. Tumor cells that acquire the ability to metabolize fructose have a fitness advantage over their neighboring cells, but the proteins that mediate fructose metabolism in this context are unknown. Here, we investigated the determinants of fructose-mediated cell proliferation.
methodsLive cell imaging and crystal violet assays were used to characterize the ability of several cell lines (RKO, H508, HepG2, Huh7, HEK293T (293T), A172, U118-MG, U87, MCF-7, MDA-MB-468, PC3, DLD1 HCT116, and 22RV1) to proliferate in fructose (i.e., the fructolytic ability). Fructose metabolism gene expression was determined by RT-qPCR and western blot for each cell line. A positive selection approach was used to "train" non-fructolytic PC3 cells to utilize fructose for proliferation. RNA-seq was performed on parental and trained PC3 cells to find key transcripts associated with fructolytic ability. A CRISPR-cas9 plasmid containing KHK-specific sgRNA was transfected in 293T cells to generate KHK
resultsWe found that neither the tissue of origin nor expression level of any single gene related to fructose catabolism determine the fructolytic ability. However, cells cultured chronically in fructose can develop fructolytic ability. SLC2A5, encoding the fructose transporter, GLUT5, was specifically upregulated in these cells. Overexpression of GLUT5 in non-fructolytic cells enabled growth in fructose-containing media across cells of different origins. GLUT5 permitted fructose to flux through glycolysis using hexokinase (HK) and not ketohexokinase (KHK).
conclusionsWe show that GLUT5 is a robust and generalizable driver of fructose-dependent cell proliferation. This indicates that fructose uptake is the limiting factor for fructose-mediated cell proliferation. We further demonstrate that cellular proliferation with fructose is independent of KHK.
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