ArticleProceedings of the National Academy of Sciences of the United States of America2016
NF-κB-driven suppression of FOXO3a contributes to EGFR mutation-independent gefitinib resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 80 citations in OpenAlex.
- Activation of the NF-κB/ALDH1A1 signaling promotes non-mutational resistance to EGFR-TKIs in non-small cell lung cancer.Oncogene · 2026Article
- MicroRNA-regulated signaling and tumor microenvironment modulation in lung cancer: mechanistic insights and translational opportunities.Cancer cell international · 2026Review
- miR-155 aberrant expression impairs tumor rejection because of its targeting of ICOSL and multiple pathways implicated in the antitumor response.Pharmacological reviews · 2026Review
- FOXO3a/miR-4259-driven LDHA expression as a key mechanism of gemcitabine sensitivity in pancreatic ductal adenocarcinoma.Cancer & metabolism · 2025Article
- MicroRNA155 in non-small cell lung cancer: a potential therapeutic target.Frontiers in oncology · 2025Review
- Methylation-modulated PFTK1 regulates gefitinib resistance via Wnt/β-catenin signaling in EGFR mutant non-small-cell lung cancer cells.Communications biology · 2024Article
- The Role of microRNA-155 as a Biomarker in Diffuse Large B-Cell Lymphoma.Biomedicines · 2024Review
- Interconnection of CD133 Stem Cell Marker with Autophagy and Apoptosis in Colorectal Cancer.International journal of molecular sciences · 2024Review
- CCKBR+ cancer cells contribute to the intratumor heterogeneity of gastric cancer and confer sensitivity to FOXO inhibition.Cell death and differentiation · 2024Article
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- Metformin Suppresses Stemness of Non-Small-Cell Lung Cancer Induced by Paclitaxel through FOXO3a.International journal of molecular sciences · 2023Article
- Multi-Anticancer Activities of Phytoestrogens in Human Osteosarcoma.International journal of molecular sciences · 2023Review
- Acquired resistance to EGFR-TKIs in NSCLC mediates epigenetic downregulation of MUC17 by facilitating NF-κB activity via UHRF1/DNMT1 complex.International journal of biological sciences · 2023Article
- The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms.Frontiers in pharmacology · 2023Review
- FOXO transcription factors as therapeutic targets in human diseases.Trends in pharmacological sciences · 2022Review
- The Role of miRNA-182 and FOXO3 Expression in Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Article
- ANGPTL1 attenuates cancer migration, invasion, and stemness through regulating FOXO3a-mediated SOX2 expression in colorectal cancer.Clinical science (London, England : 1979) · 2022Article
- miR-196a Upregulation Contributes to Gefitinib Resistance through Inhibiting GLTP Expression.International journal of molecular sciences · 2022Article
- Xprediction: Explainable EGFR-TKIs response prediction based on drug sensitivity specific gene networks.PloS one · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs, such as gefitinib or erlotinib) significantly prolongs survival time for patients with tumors harboring an activated mutation on EGFR; however, up to 40% of lung cancer patients exhibit acquired resistance to EGFR-TKIs with an unknown mechanism. FOXO3a, a transcription factor of the forkhead family, triggers apoptosis, but the mechanistic details involved in EGFR-TKI resistance and cancer stemness remain largely unclear. Here, we observed that a high level of FOXO3a was correlated with EGFR mutation-independent EGFR-TKI sensitivity, the suppression of cancer stemness, and better progression-free survival in lung cancer patients. The suppression of FOXO3a obviously increased gefitinib resistance and enhanced the stem-like properties of lung cancer cells; consistent overexpression of FOXO3a in gefitinib-resistant lung cancer cells reduced these effects. Moreover, we identified that miR-155 targeted the 3'UTR of FOXO3a and was transcriptionally regulated by NF-κB, leading to repressed FOXO3a expression and increased gefitinib resistance, as well as enhanced cancer stemness of lung cancer in vitro and in vivo. Our findings indicate that FOXO3a is a significant factor in EGFR mutation-independent gefitinib resistance and the stemness of lung cancer, and suggest that targeting the NF-κB/miR-155/FOXO3a pathway has potential therapeutic value in lung cancer with the acquisition of resistance to EGFR-TKIs.
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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.