ArticleCancer communications (London, England)2023
Blockage of EGFR/AKT and mevalonate pathways synergize the antitumor effect of temozolomide by reprogramming energy metabolism in glioblastoma.
Article in Cancer communications (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Bioenergetic Materials for Tissue Regeneration: Modulating Metabolism to Promote Cellular Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CPT1A-mediated IDO1 succinylation shapes EGFRvIII-driven resistance to tumor electric field therapy in glioblastoma.Nature communications · 2026Article
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- The Unsaturated/Saturated Fatty Acid Ratio: A Metabolic Hub and Therapeutic Vulnerability in Glioblastoma.Biomedicines · 2026Review
- Fatty acid metabolism in glioma: a review of novel targets and therapeutic strategies.Chinese neurosurgical journal · 2026Review
- ACSL3 inhibits ferroptosis in gastric cancer through the activation of unfolded protein response following endoplasmic reticulum stress.Cell death & disease · 2026Article
- MALDI-TOF Mass Spectrometry for Glioblastoma Secretome Biomarker Screening: A Review of Challenges and Perspectives.Current issues in molecular biology · 2026Review
- ErbB signaling in brain injury regeneration: Pathway interactions and therapeutic potential.Neural regeneration research · 2026Article
- CRL4EMBO reports · 2026Article
- Statins targeting mevalonate-geranylgeranyl diphosphate pathway inhibit proliferation in NK/T lymphoma by promoting pyroptosis.Translational oncology · 2026Article
- A novel risk model of cholesterol metabolism-related mRNAs for predicting overall survival and immune signature in glioma based on machine learning and multi-omics data.Translational cancer research · 2026Article
- Disrupting Akt-Wnt/β-catenin signaling suppresses glioblastoma stem cell growth and tumor progression in immunocompetent mice.Journal of neuro-oncology · 2026Article
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Review
- A multi-database pharmacovigilance study reveals distinctive immunosuppressive and opportunistic infection disproportionality signals with bevacizumab and temozolomide combination therapy in glioblastoma.Frontiers in medicine · 2026Article
- Sevoflurane is associated with reduced EGFR-VEGF-AKT signaling in glioma tissues relative to propofol: a bioinformatics and clinical pilot study.Frontiers in oncology · 2026Article
- Spinosin Suppresses RANKL-induced Osteoclastogenesis and Alleviates LPS-induced Cranial Osteolysis: A Study based on Network Pharmacology and Experimental Validation.Current medicinal chemistry · 2026Article
- Immunometabolic reprogramming of central and peripheral immune cells in mental disorders: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- KRTCAP2 accelerates malignant progression through modulating tumor cell function and M2 macrophage infiltration in glioma.Frontiers in immunology · 2026Article
- Atorvastatin as a pleiotropic anticancer agent: mechanisms, evidence, and therapeutic repurposing potential.Frontiers in immunology · 2026Review
- Nano-Enabled Fluorescence Switching: A Novel Strategy for PDGFRβ Detection and TKI Therapy Monitoring.Research (Washington, D.C.) · 2026Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
backgroundMetabolism reprogramming plays a vital role in glioblastoma (GBM) progression and recurrence by producing enough energy for highly proliferating tumor cells. In addition, metabolic reprogramming is crucial for tumor growth and immune-escape mechanisms. Epidermal growth factor receptor (EGFR) amplification and EGFR-vIII mutation are often detected in GBM cells, contributing to the malignant behavior. This study aimed to investigate the functional role of the EGFR pathway on fatty acid metabolism remodeling and energy generation.
methodsClinical GBM specimens were selected for single-cell RNA sequencing and untargeted metabolomics analysis. A metabolism-associated RTK-fatty acid-gene signature was constructed and verified. MK-2206 and MK-803 were utilized to block the RTK pathway and mevalonate pathway induced abnormal metabolism. Energy metabolism in GBM with activated EGFR pathway was monitored. The antitumor effect of Osimertinib and Atorvastatin assisted by temozolomide (TMZ) was analyzed by an intracranial tumor model in vivo.
resultsGBM with high EGFR expression had characteristics of lipid remodeling and maintaining high cholesterol levels, supported by the single-cell RNA sequencing and metabolomics of clinical GBM samples. Inhibition of the EGFR/AKT and mevalonate pathways could remodel energy metabolism by repressing the tricarboxylic acid cycle and modulating ATP production. Mechanistically, the EGFR/AKT pathway upregulated the expressions of acyl-CoA synthetase short-chain family member 3 (ACSS3), acyl-CoA synthetase long-chain family member 3 (ACSL3), and long-chain fatty acid elongation-related gene ELOVL fatty acid elongase 2 (ELOVL2) in an NF-κB-dependent manner. Moreover, inhibition of the mevalonate pathway reduced the EGFR level on the cell membranes, thereby affecting the signal transduction of the EGFR/AKT pathway. Therefore, targeting the EGFR/AKT and mevalonate pathways enhanced the antitumor effect of TMZ in GBM cells and animal models.
conclusionsOur findings not only uncovered the mechanism of metabolic reprogramming in EGFR-activated GBM but also provided a combinatorial therapeutic strategy for clinical GBM management.
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