ArticleJournal of experimental & clinical cancer research : CR2023
Toosendanin targeting eEF2 impedes Topoisomerase I & II protein translation to suppress esophageal squamous cell carcinoma growth.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- A hub for an herb: is STAT3 blockade at the epicenter of toosendanin-induced NCOA4-dependent ferritinophagy and ferroptosis in cancer cells?Journal of gastrointestinal oncology · 2026Article
- Toosendanin suppresses acute myeloid leukemia by targeting DDX5/c-Myc axis to inhibit protein synthesis.Journal of translational medicine · 2026Article
- CircPTP4A2 (hsa_circ_0007364) promotes growth and invasion of non-small cell lung cancer by regulating miR-183-5p/EEF2 axis.Scientific reports · 2026Article
- Targeting tumor-associated macrophages through phytochemicals: a promising strategy for cold tumor therapy.Chinese medicine · 2026Review
- Patient-derived xenograft models: Current status, challenges, and innovations in cancer research.Genes & diseases · 2025Review
- PLGA-based herb Toosendanin delivery system for efficient therapy of oral squamous cell carcinoma.BMC complementary medicine and therapies · 2025Article
- Toosendanin induces ferroptosis in gastrointestinal stromal tumor cells through the regulation of the NCOA4 ferritinophagy pathway: implications for tumor proliferation, migration, and invasion.Journal of gastrointestinal oncology · 2025Article
- Elongation factor 2 in cancer: a promising therapeutic target in protein translation.Cellular & molecular biology letters · 2024Review
- Ribonucleotide reductase small subunit M2 promotes the proliferation of esophageal squamous cell carcinoma cellsActa pharmaceutica Sinica. B · 2024Article
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
- Patient-derived tumor models: a suitable tool for preclinical studies on esophageal cancer.Cancer gene therapy · 2023Review
- TSN Disrupts Fanconi Anemia Pathway Activation Through JAK/STAT1-Mediated Transcriptional Repression of FA Core Subunits in Bladder Cancer.Dose-response : a publication of International Hormesis SocietyArticle
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAlthough molecular targets such as HER2, TP53 and PIK3CA have been widely studied in esophageal cancer, few of them were successfully applied for clinical treatment. Therefore, it is urgent to discover novel actionable targets and inhibitors. Eukaryotic translational elongation factor 2 (eEF2) is reported to be highly expressed in various cancers. However, its contribution to the maintenance and progression of cancer has not been fully clarified.
methodsIn the present study, we utilized tissue array to evaluate eEF2 protein expression and clinical significance in esophageal squamous cell carcinoma (ESCC). Next, we performed knockdown, overexpression, RNA-binding protein immunoprecipitation (RIP) sequence, and nascent protein synthesis assays to explore the molecular function of eEF2. Furthermore, we utilized compound screening, Surface Plasmon Resonance (SPR), Isothermal Titration Calorimetry (ITC) assay, cell proliferation and Patient derived xenograft (PDX) mouse model assays to discover an eEF2 inhibitor and assess its effects on ESCC growth.
resultsWe found that eEF2 were highly expressed in ESCC and negatively associated with the prognosis of ESCC patients. Knocking down of eEF2 suppressed the cell proliferation and colony formation of ESCC. eEF2 bond with the mRNA of Topoisomerase II (TOP1) and Topoisomerase II (TOP2) and enhanced the protein biosynthesis of TOP1 and TOP2. We also identified Toosendanin was a novel inhibitor of eEF2 and Toosendanin inhibited the growth of ESCC in vitro and in vivo.
conclusionsOur findings show that Toosendanin treatment suppresses ESCC growth through targeting eEF2 and regulating downstream TOP1 and TOP2 biosynthesis. eEF2 could be supplied as a potential therapeutic target in the further clinical studies.
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