ArticleJournal for immunotherapy of cancer2022
eEF2K promotes PD-L1 stabilization through inactivating GSK3β in melanoma.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pooled it
- FAM83D facilitates EMT and metastasis of cervical cancer via interaction with GSK3β and inactivation of GSK3β/stabilization of Snail signaling.Biology direct · 2026Article
- 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
- Integrative analysis and experiments to explore GAS1 as a prognostic target for ovarian cancer based on angiogenesis-related genes.Journal of ovarian research · 2025Article
- Prediction of neoadjuvant chemotherapy efficacy in patients with HER2-low breast cancer based on ultrasound radiomics.Cancer imaging : the official publication of the International Cancer Imaging Society · 2025Article
- Novel NIR fluorescent probe IR-546 inhibits melanoma through the AKT/GSK3β/β-catenin pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Article
- PD-L1 siRNA incorporation into a cationic liposomal tumor mRNA vaccine enhances cytotoxic T cell activation and prevents immune evasion.Materials today. Bio · 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
- Advanced pathological subtype classification of thyroid cancer using efficientNetB0.Diagnostic pathology · 2025Article
- eEF2K alleviates doxorubicin-induced cardiotoxicity by inhibiting GSK3β and improving autophagy dysfunction.Cell biology and toxicology · 2024Article
- Rhaponticin suppresses the stemness phenotype of gastric cancer stem-like cells CD133+/CD166 + by inhibiting programmed death-ligand 1.BMC gastroenterology · 2024Article
- Isobutyric Acid Promotes Immune Evasion in Colorectal Cancer via Increased PD-L1 Expression.Cancer medicine · 2024Article
- CD38 symmetric dimethyl site R58 promotes malignant tumor cell immune escape by regulating the cAMP-GSK3β-PD-L1 axis.Heliyon · 2024Article
- Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide.Cell & bioscience · 2024Article
- Challenges coexist with opportunities: development of a macrocyclic peptide PET radioligand for PD-L1.European journal of nuclear medicine and molecular imaging · 2024Article
- Benzosceptrin C induces lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting DHHC3.Cell reports. Medicine · 2024Article
- Development of novel peptide-based radiotracers for detecting PD-L1 expression and guiding cancer immunotherapy.European journal of nuclear medicine and molecular imaging · 2024Article
- Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint blockade (ICB) targeting programmed death ligand-1 (PD-L1)/programmed cell death protein-1 (PD-1) pathway has become an attractive strategy for cancer treatment; however, unsatisfactory efficacy has limited its clinical benefits. Therefore, a more comprehensive understanding of the regulation of PD-L1 expression is essential for developing more effective cancer immunotherapy. Recent studies have revealed the important roles of eukaryotic elongation factor 2 kinase (eEF2K) in promoting epithelial-mesenchymal transition (EMT), angiogenesis, tumor cell migration and invasion; nevertheless, the exact role of eEF2K in the regulation of tumor immune microenvironment (TIME) remains largely unknown.
methodsIn this study, we used a cohort of 38 patients with melanoma who received anti-PD-1 treatment to explore the association between eEF2K expression and immunotherapy efficacy against melanoma. Immunoprecipitation-mass spectrometry analysis and in vitro assays were used to examine the role and molecular mechanism of eEF2K in regulating PD-L1 expression. We also determined the effects of eEF2K on tumor growth and cytotoxicity of CD8
resultsHigh eEF2K expression is correlated with better therapeutic response and longer survival in patients with melanoma treated with PD-1 monoclonal antibody (mAb). Moreover, eEF2K protein expression is positively correlated with PD-L1 protein expression. Mechanistically, eEF2K directly bound to and inactivated glycogen synthase kinase 3 beta (GSK3β) by phosphorylating it at serine 9 (S9), leading to PD-L1 protein stabilization and upregulation, and subsequently tumor immune evasion. Knockdown of eEF2K decreased PD-L1 expression and enhanced CD8
conclusionsOur results suggest that eEF2K may serve as a biomarker for predicting therapeutic response and prognosis in patients receiving anti-PD-1 therapy, reveal a vital role of eEF2K in regulating TIME by controlling PD-L1 expression and provide a potential combination therapeutic strategy of eEF2K inhibition with ICB therapy.
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