ArticleEBioMedicine2019
FoxO3a inhibiting expression of EPS8 to prevent progression of NSCLC: A new negative loop of EGFR signaling.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- hsa_circ_0008758 Activates the MDM2/FOXO3a/PGK1 Pathway Through the miR-361-3p/SPIN1 Axis to Promote the Warburg Effect of Non-Small Cell Lung Cancer.Tissue engineering and regenerative medicine · 2026Article
- CircFoxo3 knockdown inhibit gastric cancer progression by regulating Foxo3.In vitro cellular & developmental biology. Animal · 2026Article
- Lung adenocarcinoma surfaceome remodeling with EGFR inhibitors uncovers placental alkaline phosphatase as a target for combination therapy.Cell reports. Medicine · 2025Article
- The cell autonomous and non-autonomous functions of Rab27 in longevity and neuroprotection inAutophagy · 2025Article
- EFEMP1-Mediated Regulation of Choroidal Vascular Dysfunction in Myopia: Insights Into the FOXO3/VEGFA Pathway as a Therapeutic Target.Investigative ophthalmology & visual science · 2025Article
- Forkhead Box O (FOXO) signaling in NSCLC: pathways to targeted therapies.EXCLI journal · 2024Article
- Bioinformatics analysis and experimental verification of TIGD1 in non-small cell lung cancer.Frontiers in medicine · 2024Article
- Knockdown of EPS8 expression attenuates the proliferation of enzalutamide-resistant prostate cancer cells.American journal of cancer research · 2024Article
- Loss of EPS8 sensitizes non-small-cell lung carcinoma to chemotherapy-induced DNA damage.Cancer gene therapy · 2023Article
- Effects and mechanisms of Eps8 on the biological behaviour of malignant tumours (Review).Oncology reports · 2021Review
- Knockdown of hsa_circ_0000729 Inhibits the Tumorigenesis of Non-Small Cell Lung Cancer Through Mediation of miR-1281/FOXO3 Axis.Cancer management and research · 2021Article
- Serum and Glucocorticoid-Inducible Kinase 1 (SGK1) in NSCLC Therapy.Pharmaceuticals (Basel, Switzerland) · 2020Review
- TNNC1 Reduced Gemcitabine Sensitivity of Nonsmall-Cell Lung Cancer by Increasing Autophagy.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Dexmedetomidine suppresses the progression of esophageal cancer via miR-143-3p/epidermal growth factor receptor pathway substrate 8 axis.Anti-cancer drugs · 2020Article
- Exosomes Carrying MicroRNA-155 Target Forkhead Box O3 of Endothelial Cells and Promote Angiogenesis in Gastric Cancer.Molecular therapy oncolytics · 2019Article
- Article
- EPS8 Differentially Regulates Antioxidant Defense and Mitochondrial Homeostatic Signaling in LNCaP and Enzalutamide-resistant LNCaP Cells.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe resistance to EGF receptor (EGFR) tyrosine kinase inhibitors (TKI) is a major challenge in the treatment of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms behind resistance is therefore an important issue. Here we assessed the role of EGFR pathway substrate 8 (EPS8) and Forkhead box O 3a (FoxO3a) as potentially valuable targets in the resistance of NSCLC .
methodsThe expression levels of EPS8 and FoxO3a in patients with NSCLC (n = 75) were examined by immunohistochemistry staining, while in cells were detected by qPCR and western blot. The effects of EPS8 and FoxO3a on resistance, migration and invasion, cell cycle arrest were detected by MTT, transwell and flow cytometry, respectively. Chromatin immunoprecipitation and luciferase reporter assays were performed to determine the mechanisms of EPS8 expression and FoxO3a regulation.
findingsWe observed that the expression of EPS8 inversely correlated with FoxO3a in NSCLC cell lines and NSCLC patients. FoxO3a levels were significantly decreased in tumor tissues compared with para-carcinoma tissues, while EPS8 is opposite. Besides, they play reverse roles in the resistance to gefitinib, the migration and invasion abilities, the cell cycle arrest in vitro and the tumor growth in vivo. Mechanistically, FoxO3a inhibits EPS8 levels by directly binding its gene promoter and they form a negative loop in EGFR pathway.
interpretationTargeting FoxO3a and EPS8 in EGFR signaling pathway prevents the progression of NSCLC, which implied that the negative loop they formed could served as a therapeutic target for overcoming resistance in NSCLC. FUNDS: National Natural Science Foundation of China, Science and Technology Project of Henan, Outstanding Young Talent Research Fund of Zhengzhou University and the National Scholarship Fund.
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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.