ArticleThe Journal of biological chemistry2015
Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 186 citations in OpenAlex.
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- Association between the presence of EGFR or ALK mutations and the location of primary non-small cell lung cancer, as well as metabolic activity observed onOncology letters · 2026Article
- Everolimus suppresses glucose transporter 3 membrane trafficking to improve therapeutic efficacy of umbilical cord blood-derived mesenchymal stem cell transplantation in diabetic retinopathy.Cell death & disease · 2026Article
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- SMAD3 and HIF-1α orchestrate metabolic transition to aerobic glycolysis as a critical prerequisite for spontaneous reprogramming of spermatogonial stem cells.Stem cell research & therapy · 2025Article
- EGFR controls transcriptional and metabolic rewiring in KRASEMBO molecular medicine · 2025Article
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
- Fuel for thought: targeting metabolism in lung cancer.Translational lung cancer research · 2024Review
- Tumor-related fungi and crosstalk with gut fungi in the tumor microenvironment.Cancer biology & medicine · 2024Review
- Understanding serine and glycine metabolism in cancer: a path towards precision medicine to improve patient's outcomes.Discover oncology · 2024Review
- Glutamine and serum starvation alters the ATP production, oxidative stress, and abundance of mitochondrial RNAs in extracellular vesicles produced by cancer cells.Scientific reports · 2024Article
- Growth Signaling Networks Orchestrate Cancer Metabolic Networks.Cold Spring Harbor perspectives in medicine · 2024Review
- Chrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex.Cancer cell international · 2024Article
- A PET-Surrogate Signature for the Interrogation of the Metabolic Status of Breast Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Rational combination platform trial design for children and young adults with diffuse midline glioma: A report from PNOC.Neuro-oncology · 2024Article
- The molecular subtyping and precision medicine in triple-negative breast cancer---based on Fudan TNBC classification.Cancer cell international · 2024Review
- Exploring acenocoumarol and silodosin in non-small cell lung cancer: Insights into EGFR-linked signaling mechanisms.F1000Research · 2024Article
- Phytochemicals Target Multiple Metabolic Pathways in Cancer.Antioxidants (Basel, Switzerland) · 2023Review
56 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic epidermal growth factor receptor (EGFR) signaling plays an important role in regulating global metabolic pathways, including aerobic glycolysis, the pentose phosphate pathway (PPP), and pyrimidine biosynthesis. However, the molecular mechanism by which EGFR signaling regulates cancer cell metabolism is still unclear. To elucidate how EGFR signaling is linked to metabolic activity, we investigated the involvement of the RAS/MEK/ERK and PI3K/AKT/mammalian target of rapamycin (mTOR) pathways on metabolic alteration in lung adenocarcinoma (LAD) cell lines with activating EGFR mutations. Although MEK inhibition did not alter lactate production and the extracellular acidification rate, PI3K/mTOR inhibitors significantly suppressed glycolysis in EGFR-mutant LAD cells. Moreover, a comprehensive metabolomics analysis revealed that the levels of glucose 6-phosphate and 6-phosphogluconate as early metabolites in glycolysis and PPP were decreased after inhibition of the PI3K/AKT/mTOR pathway, suggesting a link between PI3K signaling and the proper function of glucose transporters or hexokinases in glycolysis. Indeed, PI3K/mTOR inhibition effectively suppressed membrane localization of facilitative glucose transporter 1 (GLUT1), which, instead, accumulated in the cytoplasm. Finally, aerobic glycolysis and cell proliferation were down-regulated when GLUT1 gene expression was suppressed by RNAi. Taken together, these results suggest that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells.
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