ArticleOncogene2016
eEF-2 kinase is a critical regulator of Warburg effect through controlling PP2A-A synthesis.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Targeted Degradation of eEF2K by a Structure-Guided PROTAC Strategy for the Treatment of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- eEF2K-Mediated Stabilization of PCBP2 Promotes Oncogenic mRNA Programs in Triple-Negative Breast Cancer.International journal of biological sciences · 2026Article
- Triptolide targets PPP2CA/ITGA5 axis to suppress lactate-driven ovarian cancer progression.Chinese medicine · 2025Article
- eEF2K is a poor prognostic factor and novel molecular target in pancreatic cancer: regulating tumor growth and progression via the tumor microenvironment.Cell death & disease · 2025Article
- Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.ACS omega · 2024Review
- eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design.Molecules (Basel, Switzerland) · 2023Review
- Tumorous expression of NAC1 restrains antitumor immunity through the LDHA-mediated immune evasion.Journal for immunotherapy of cancer · 2022Article
- Targeting Protein Translation in Melanoma by Inhibiting EEF-2 Kinase Regulates Cholesterol Metabolism though SREBP2 to Inhibit Tumour Development.International journal of molecular sciences · 2022Article
- eEF2K promotes PD-L1 stabilization through inactivating GSK3β in melanoma.Journal for immunotherapy of cancer · 2022Article
- Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8Science advances · 2022Article
- EEF2K silencing inhibits tumour progression through repressing SPP1 and synergises with BET inhibitors in melanoma.Clinical and translational medicine · 2022Article
- Increased eEF2K Promotes Glycolysis and Aggressive Behaviors of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.Journal of inflammation research · 2022Article
- Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel EF2 Kinase Inhibitor Suppresses Breast Cancer GrowthACS pharmacology & translational science · 2021Article
- Dexamethasone Conjugates: Synthetic Approaches and Medical Prospects.Biomedicines · 2021Review
- Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy.International journal of molecular sciences · 2021Review
- Combined treatment of mitoxantrone sensitizes breast cancer cells to rapalogs through blocking eEF-2K-mediated activation of Akt and autophagy.Cell death & disease · 2020Article
- Control of translation elongation in health and disease.Disease models & mechanisms · 2020Review
- PP2A Deficiency Enhances Carcinogenesis of Lgr5Cells · 2019Article
- Chemoproteomic Discovery of a Ritanserin-Targeted Kinase Network Mediating Apoptotic Cell Death of Lung Tumor Cells.Molecular pharmacology · 2018Article
- Eukaryotic Elongation Factor 2 Kinase (eEF2K) in Cancer.Cancers · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
Cancer cells predominantly metabolize glucose by glycolysis to produce energy in order to meet their metabolic requirement, a phenomenon known as Warburg effect. Although Warburg effect is considered a peculiarity critical for survival and proliferation of cancer cells, the regulatory mechanisms behind this phenomenon remain incompletely understood. We report here that eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, has a critical role in promoting glycolysis in cancer cells. We showed that deficiency in eEF-2K significantly reduced the uptake of glucose and decreased the productions of lactate and adenosine triphosphate in tumor cells and in the Ras-transformed mouse embryonic fibroblasts. We further demonstrated that the promotive effect of eEF-2K on glycolysis resulted from the kinase-mediated restriction of synthesis of the protein phosphatase 2A-A (PP2A-A), a key factor that facilitates the ubiquitin-proteasomal degradation of c-Myc protein, as knockdown of eEF-2K expression led to a significant increase in PP2A-A protein synthesis and remarkable downregulation of c-Myc and pyruvate kinase M2 isoform, the key glycolytic enzyme transcriptionally activated by c-Myc. In addition, depletion of eEF-2K reduced the ability of the transformed cells to proliferate and enhanced the sensitivity of tumor cells to chemotherapy both in vitro and in vivo. These results, which uncover a role of the eEF-2K-mediated control of PP2A-A in tumor cell glycolysis, provide new insights into the regulation of the Warburg effect.
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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.