ArticleCell communication and signaling : CCS2020
The eEF2 kinase-induced STAT3 inactivation inhibits lung cancer cell proliferation by phosphorylation of PKM2.
Article in Cell communication and signaling : CCS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- The PI3K/AKT signaling networks in cancer glucose metabolism: mechanisms and therapeutic implications.Translational oncology · 2026Review
- Promising Role of PKM2 in the Diagnosis and Prognosis of Ovarian Cancer.Anti-cancer agents in medicinal chemistry · 2026Review
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Article
- Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans.Nature communications · 2025Article
- Branched-Chain Amino Acids Target miR-203a/fosb Axis to Promote Skeletal Muscle Growth in Common Carp (Aquaculture nutrition · 2025Article
- A novel basement membrane-related gene signature predicts prognosis and immunotherapy response in hepatocellular carcinoma.Frontiers in oncology · 2024Article
- Control of CD4Signal transduction and targeted therapy · 2023Article
- Impact of silencing eEF2K expression on the malignant properties of chordoma.Molecular biology reports · 2023Article
- Regulation of ErbB Receptors by the CaBiomedicines · 2023Review
- Functions and modulation of PKM2 activity by human papillomavirus E7 oncoprotein (Review).Oncology letters · 2023Review
- EEF2K silencing inhibits tumour progression through repressing SPP1 and synergises with BET inhibitors in melanoma.Clinical and translational medicine · 2022Article
- TRPM7 silencing modulates glucose metabolic reprogramming to inhibit the growth of ovarian cancer by enhancing AMPK activation to promote HIF-1α degradation.Journal of experimental & clinical cancer research : CR · 2022Article
- Salvianolic Acid B Suppresses Non-Small-Cell Lung Cancer Metastasis through PKM2-Independent Metabolic Reprogramming.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Increased eEF2K Promotes Glycolysis and Aggressive Behaviors of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.Journal of inflammation research · 2022Article
- Phosphoproteomics: a valuable tool for uncovering molecular signaling in cancer cells.Expert review of proteomics · 2021Review
- Article
- TSHZ2 is an EGF-regulated tumor suppressor that binds to the cytokinesis regulator PRC1 and inhibits metastasis.Science signaling · 2021Article
- The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs.International journal of molecular sciences · 2021Review
- Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase.Frontiers in molecular biosciences · 2021Review
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEukaryotic elongation factor-2 kinase (eEF2K) is a Ca 2+ /calmodulin (CaM)-dependent protein kinase that inhibits protein synthesis. However, the role of eEF2K in cancer development was reported paradoxically and remains to be elucidated.
methodsHerein, A549 cells with eEF2K depletion or overexpression by stably transfected lentivirus plasmids were used in vitro and in vivo study. MTT and colony assays were used to detect cell proliferation and growth. Extracellular glucose and lactate concentration were measured using test kit. Immunoblot and co-immunoprecipitation assays were used to examine the molecular biology changes and molecular interaction in these cells. LC-MS/MS analysis and [γ- 32 P] ATP kinase assay were used to identify combining protein and phosphorylation site. Nude mice was utilized to study the correlation of eEF2K and tumor growth in vivo.
resultsWe demonstrated that eEF2K inhibited lung cancer cells proliferation and affected the inhibitory effects of EGFR inhibitor gefitinib. Mechanistically, we showed that eEF2K formed a complex with PKM2 and STAT3, thereby phosphorylated PKM2 at T129, leading to reduced dimerization of PKM2. Subsequently, PKM2 impeded STAT3 phosphorylation and STAT3-dependent c-Myc expression. eEF2K depletion promoted the nuclear translocation of PKM2 and increased aerobic glycolysis reflected by increased lactate secretion and glucose.
conclusionsOur findings define a novel mechanism underlying the regulation of cancer cell proliferation by eEF2K independent of its role in protein synthesis, disclosing the diverse roles of eEF2K in cell biology, which lays foundation for the development of new anticancer therapeutic strategies.
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