ArticleBritish journal of cancer2018
Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival.
Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Can plitidepsin be used as an antiviral against RSV?mSphere · 2025Article
- SYVN1 aggravates esophageal squamous cell carcinoma development by activating NF-κB pathway to facilitate macrophage M2 polarization.Journal of thoracic disease · 2025Article
- A comprehensive analysis of the relationship between inflammasomes and autophagy in human tumors: Recent developments.Journal of cell communication and signaling · 2025Review
- Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways.International journal of molecular sciences · 2025Review
- EEF1A2 identified as a hub gene associated with the severity of metabolic dysfunction-associated steatotic liver disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- eEF1α2 is required for actin cytoskeleton homeostasis in the aging muscle.Disease models & mechanisms · 2024Article
- Plitidepsin as an Immunomodulator against Respiratory Viral Infections.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- EEF1A2 promotes HIF1A mediated breast cancer angiogenesis in normoxia and participates in a positive feedback loop with HIF1A in hypoxia.British journal of cancer · 2024Article
- Oncogenic activation of EEF1A2 expression: a journey from a putative to an established oncogene.Cellular & molecular biology letters · 2024Review
- Loss of NSUN6 inhibits osteosarcoma progression by downregulating EEF1A2 expression and activation of Akt/mTOR signaling pathway via mExperimental and therapeutic medicine · 2023Article
- Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art.International journal of molecular sciences · 2023Review
- Site-directed late-stage diversification of macrocyclic nannocystins facilitating anticancer SAR and mode of action studies.RSC medicinal chemistry · 2023Article
- Overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins to promote corticospinal axon repair after injury.Cell death discovery · 2022Article
- Direct and indirect effects of IFN-α2b in malignancy treatment: not only an archer but also an arrow.Biomarker research · 2022Review
- EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling.British journal of cancer · 2021Article
- Effect of activation of the Akt/mTOR signaling pathway by EEF1A2 on the biological behavior of osteosarcoma.Annals of translational medicine · 2021Article
- Tumor suppressor DRD2 facilitates M1 macrophages and restricts NF-κB signaling to trigger pyroptosis in breast cancer.Theranostics · 2021Article
- Exploration of the Modulatory Property Mechanism of ELeng Capsule in the Treatment of Endometriosis Using Transcriptomics Combined With Systems Network Pharmacology.Frontiers in pharmacology · 2021Article
- Article
- Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue.Cancers · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThrough several not-fully-characterised moonlighting functions, translation elongation factor eEF1A2 is known to provide a fitness boost to cancer cells. Furthermore, eEF1A2 has been demonstrated to confer neoplastic characteristics on preneoplastic, nontumourigenic precursor cells. We have previously shown that eEF1A2 is the target of plitidepsin, a marine drug currently in development for cancer treatment. Herein, we characterised a new signalling pathway through which eEF1A2 promotes tumour cell survival.
methodsPreviously unknown binding partners of eEF1A2 were identified through co-immunoprecipitation, high-performance liquid chromatography-mass spectrometry and proximity ligation assay. Using plitidepsin to release eEF1A2 from those protein complexes, their effects on cancer cell survival were analysed in vitro.
resultsWe uncovered that double-stranded RNA-activated protein kinase (PKR) is a novel eEF1A2-interacting partner whose pro-apoptotic effect is hindered by the translation factor, most likely through sequestration and inhibition of its kinase activity. Targeting eEF1A2 with plitidepsin releases PKR from the complex, facilitating its activation and triggering a mitogen-activated protein kinase signalling cascade together with a nuclear factor-κB-dependent activation of the extrinsic apoptotic pathway, which lead to tumour cell death.
conclusionsThrough its binding to PKR, eEF1A2 provides a survival boost to cancer cells, constituting an Achilles heel that can be exploited in anticancer therapy.
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