ArticleClinical and translational medicine2022
EEF2K silencing inhibits tumour progression through repressing SPP1 and synergises with BET inhibitors in melanoma.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- A systematic review of progress toward unlocking the power of epigenetics in breast cancer: latest updates and perspectives.Frontiers in pharmacology · 2025Pooled it
- The crucial role of SPP1 in osteoporosis, osteoarthritis, and cancer.Pharmaceutical science advances · 2025Review
- Characterization of Early Metastatic Subpopulations in Uveal Melanoma: Single-Cell Insights Into SPP1+ Cells and Their Interactions With Macrophages.Investigative ophthalmology & visual science · 2025Article
- Understanding the complexity of tumor-associated macrophages: Druggable and therapeutic insights.Acta pharmaceutica Sinica. B · 2025Review
- Development and Validation of an Extracellular Matrix Gene Expression Signature for Prognostic Prediction in Patients with Uveal Melanoma.International journal of molecular sciences · 2025Article
- Identification of a Novel Substrate for eEF2K and the AURKA-SOX8 as the Related Pathway in TNBC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- VSIG4Journal of experimental & clinical cancer research : CR · 2025Article
- SPP1, LYZ, and MCM5: potential diagnostic biomarkers for rheumatoid arthritis and cervical cancer comorbidity.Frontiers in medicine · 2025Article
- eEF-2K Deficiency Boosts the Virus-Specific Effector CD8Viruses · 2024Article
- Propafenone facilitates mitochondrial-associated ferroptosis and synergizes with immunotherapy in melanoma.Journal for immunotherapy of cancer · 2024Article
- Single-Nuclei Transcriptome Profiling Reveals Intra-Tumoral Heterogeneity and Characterizes Tumor Microenvironment Architecture in a Murine Melanoma Model.International journal of molecular sciences · 2024Article
- Article
- POSTNJournal for immunotherapy of cancer · 2024Article
- Deciphering Immune Landscape Remodeling Unravels the Underlying Mechanism for Synchronized Muscle and Bone Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- Control of CD4Signal transduction and targeted therapy · 2023Article
- Inhibiting SCD expression by IGF1R during lorlatinib therapy sensitizes melanoma to ferroptosis.Redox biology · 2023Article
- BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression.Experimental & molecular medicine · 2023Article
- Regulation of post-translational modification of PD-L1 and advances in tumor immunotherapy.Frontiers in immunology · 2023Review
- EEF2K silencing inhibits tumour progression through repressing SPP1 and synergises with BET inhibitors in melanoma.Clinical and translational medicine · 2022Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundDespite the remarkable breakthroughs achieved in the management of metastatic melanoma using immunotherapy and targeted therapies, long-term clinical efficacy is often compromised due to dose-limiting toxicity and innate or acquired resistance. Therefore, it is of vital importance to further explore the molecular mechanisms underlying melanoma progression and identify new targeted therapeutic approaches.
methodsThe function of eukaryotic elongation factor-2 kinase (EEF2K) in melanoma were investigated in vitro and in vivo. RNA-seq and chromatin immunoprecipitation (ChIP) assay were undertaken to explore the mechanisms. The antitumor effect of bromodomain and extra terminal domain (BET) inhibitors combined with cytarabine were assessed in melanoma both in vitro and in vivo.
resultsEEF2K silencing markedly attenuated the malignant phenotypes of melanoma cells, including proliferation, migration, invasion and metastasis. In contrast, EEF2K overexpression promoted melanoma cell proliferation, migration and invasion. Mechanistically, we demonstrated that EEF2K upregulates the phosphorylation of STAT3 (p-STAT3) at Tyr705, which binds to the promoter region of SPP1 and enhances its transcription, thus facilitating melanoma progression. Transfection-induced re-expression of SPP1 partly negated the inhibitory effect of EEF2K silencing on melanoma, whereas inhibition of SPP1 or STAT3 significantly abolished the efficacy of EEF2K on melanoma cells. Intriguingly, EEF2K silencing combined with BET inhibitor treatment further inhibited cell proliferation and promoted apoptosis in melanoma. We further screened the US FDA-approved antitumour drug library and identified cytarabine as a potential clinically applicable EEF2K inhibitor that could synergise with BET inhibitors in melanoma treatment.
conclusionEEF2K/p-STAT3/SPP1 may be a novel oncogenic pathway in melanoma progression, which could be a target for novel combination therapy for melanoma.
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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.