ArticlePloS one2015
Tumor cells switch to mitochondrial oxidative phosphorylation under radiation via mTOR-mediated hexokinase II inhibition--a Warburg-reversing effect.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 125 citations in OpenAlex.
- Lactate-Mediated Lysine Lactylation in Renal Fibrosis: Current Progress and Challenges.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Marbofloxacin Suppresses Breast Cancer Growth Through Oxidative Stress and Metabolic Reprogramming with Predicted HSP90AA1-EGFR Network Modulation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Nutritional Status-Based Model for Predicting Low-Lactate Shock: A Retrospective Cohort Study.Shock (Augusta, Ga.) · 2026Article
- Inhibition of mitochondrial RNA polymerase sensitizes cancer cells to radiation by inhibiting mitochondrial respiration.Journal of radiation research · 2026Article
- The eIF3a/m6A/ENO1 axis orchestrates glycolytic reprogramming and cell growth in cervical cancer.Journal of bioenergetics and biomembranes · 2026Article
- The Warburg Effect and Aerobic Glycolysis in Tumors.Cancer treatment and research · 2026Review
- Glutamine Metabolism: Role in Cancer Cell Proliferation and Survival.Cancer treatment and research · 2026Review
- ENO1 Knockdown Impedes Tumour Progression and Promotes Oxidative Phosphorylation in Cutaneous Squamous Cell Carcinoma.Acta dermato-venereologica · 2025Article
- Early metabolic reprogramming and carbonic anhydrase IX-mediated extracellular acidification drive radiotherapy-induced glioblastoma cell dedifferentiation.Acta neuropathologica communications · 2025Article
- Metabolic Plasticity and Cancer Stem Cell Metabolism: Exploring the Glycolysis-OXPHOS Switch as a Mechanism for Resistance and Tumorigenesis.Stem cell reviews and reports · 2025Review
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
- Glucose Metabolism and Tumor Microenvironment: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Metabolic Reprogramming at the Edge of Redox: Connections Between Metabolic Reprogramming and Cancer Redox State.International journal of molecular sciences · 2025Review
- Current Trends and Challenges in Targeting Tumor Mitochondrial Glycolysis and Oxidative Phosphorylation Pathways for Cancer Therapy.Current protein & peptide science · 2025Article
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
- Targeting Radiation Resistance in Oesophageal Adenocarcinoma with Pyrazinib-Functionalised Gold Nanoparticles.Cancers · 2024Article
- The deubiquitinase Ubp3/Usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting.eLife · 2024Article
- Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy.Cancer research communications · 2024Article
- Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Nano-Assisted Radiotherapy Strategies: New Opportunities for Treatment of Non-Small Cell Lung Cancer.Research (Washington, D.C.) · 2024Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A unique feature of cancer cells is to convert glucose into lactate to produce cellular energy, even under the presence of oxygen. Called aerobic glycolysis [The Warburg Effect] it has been extensively studied and the concept of aerobic glycolysis in tumor cells is generally accepted. However, it is not clear if aerobic glycolysis in tumor cells is fixed, or can be reversed, especially under therapeutic stress conditions. Here, we report that mTOR, a critical regulator in cell proliferation, can be relocated to mitochondria, and as a result, enhances oxidative phosphorylation and reduces glycolysis. Three tumor cell lines (breast cancer MCF-7, colon cancer HCT116 and glioblastoma U87) showed a quick relocation of mTOR to mitochondria after irradiation with a single dose 5 Gy, which was companied with decreased lactate production, increased mitochondrial ATP generation and oxygen consumption. Inhibition of mTOR by rapamycin blocked radiation-induced mTOR mitochondrial relocation and the shift of glycolysis to mitochondrial respiration, and reduced the clonogenic survival. In irradiated cells, mTOR formed a complex with Hexokinase II [HK II], a key mitochondrial protein in regulation of glycolysis, causing reduced HK II enzymatic activity. These results support a novel mechanism by which tumor cells can quickly adapt to genotoxic conditions via mTOR-mediated reprogramming of bioenergetics from predominantly aerobic glycolysis to mitochondrial oxidative phosphorylation. Such a "waking-up" pathway for mitochondrial bioenergetics demonstrates a flexible feature in the energy metabolism of cancer cells, and may be required for additional cellular energy consumption for damage repair and survival. Thus, the reversible cellular energy metabolisms should be considered in blocking tumor metabolism and may be targeted to sensitize them in anti-cancer therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.