ArticleJournal of experimental & clinical cancer research : CR2023
AMPK-HIF-1α signaling enhances glucose-derived de novo serine biosynthesis to promote glioblastoma growth.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 66 citations in OpenAlex.
- Review
- All-Trans Retinoic Acid and Curcumin Exhibit Hormesis or Synergistic Anticancer Effects in U87 Glioblastoma Cells: Defining the Proteome Accompanying Synergism.International journal of molecular sciences · 2026Article
- Engineered Cyanobacteria-Hydrogel Microecological System for Oxygen Reprogramming Synergizes Immunomodulation With Anabolism in Osteoarthritis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The dual role of AMPK in cancer metabolic reprogramming.Molecular biology reports · 2026Review
- Macrophage-to-myofibroblast transition-derived itaconate promotes bone metastasis in lung cancer through targeting of HSPA8.Experimental & molecular medicine · 2026Article
- Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease.The Journal of biological chemistry · 2026Review
- Glucose Transporter 1 in Health and Disease.MedComm · 2026Review
- Putative glioblastoma origin-like cells in the subventricular zone: isolation and characterization.Experimental & molecular medicine · 2026Article
- PSPH Promotes Hepatocellular Carcinoma Progression by Upregulating HIF-1α and Is Regulated by LncRNA GSEC/miR-101-3p.Current issues in molecular biology · 2026Article
- Hypoxia-induced circSPECC1 drives temozolomide resistance in glioblastoma via IGF2BP2-mediated PGK1 mRNA stabilization.Cell death & disease · 2026Article
- Bidirectional Feedback Between Metabolic Reprogramming and Epithelial-Mesenchymal Transition: From Mechanisms to Therapeutic Interventions.Molecules (Basel, Switzerland) · 2026Review
- Microstructural MRI combined with metabolic MRI to evaluate the progression-free survival of patients with glioblastoma at the early follow-up after tumor treating fields: a pilot study.BMC medical imaging · 2026Article
- Integrating Molecular Pathology, Tumor Microenvironment, and Novel Therapies to Overcome Resistance in Glioblastoma.Journal of molecular neuroscience : MN · 2026Review
- Review
- Involvement of trimethylamine N-oxide in major depressive disorder via astrocytic d-Serine dysregulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Acriflavine-empowered IR780-PTX albumin nanoparticles for reinforced synergistic photochemotherapy.Advanced biotechnology · 2026Article
- SHMT2 inhibition triggers mitochondrial apoptosis to suppress lung adenocarcinoma progression.Journal of translational medicine · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- From Cerebrovascular Injury to Brain Cancer: The Role of Blood-Brain Barrier Dysfunction.Biomedicines · 2026Review
- RNA-binding activity of PHGDH drives amyloid-beta production in a human brain organoid model of sporadic Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundCancer cells undergo cellular adaptation through metabolic reprogramming to sustain survival and rapid growth under various stress conditions. However, how brain tumors modulate their metabolic flexibility in the naturally serine/glycine (S/G)-deficient brain microenvironment remain unknown.
methodsWe used a range of primary/stem-like and established glioblastoma (GBM) cell models in vitro and in vivo. To identify the regulatory mechanisms of S/G deprivation-induced metabolic flexibility, we employed high-throughput RNA-sequencing, transcriptomic analysis, metabolic flux analysis, metabolites analysis, chromatin immunoprecipitation (ChIP), luciferase reporter, nuclear fractionation, cycloheximide-chase, and glucose consumption. The clinical significances were analyzed in the genomic database (GSE4290) and in human GBM specimens.
resultsThe high-throughput RNA-sequencing and transcriptomic analysis demonstrate that the de novo serine synthesis pathway (SSP) and glycolysis are highly activated in GBM cells under S/G deprivation conditions. Mechanistically, S/G deprivation rapidly induces reactive oxygen species (ROS)-mediated AMP-activated protein kinase (AMPK) activation and AMPK-dependent hypoxia-inducible factor (HIF)-1α stabilization and transactivation. Activated HIF-1α in turn promotes the expression of SSP enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH). In addition, the HIF-1α-induced expression of glycolytic genes (GLUT1, GLUT3, HK2, and PFKFB2) promotes glucose uptake, glycolysis, and glycolytic flux to fuel SSP, leading to elevated de novo serine and glycine biosynthesis, NADPH/NADP
conclusionOur findings reveal that metabolic stress-enhanced glucose-derived de novo serine biosynthesis is a critical metabolic feature of GBM cells, and highlight the potential to target SSP for treating human GBM.
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