ArticleCell death & disease2018
APE1 stimulates EGFR-TKI resistance by activating Akt signaling through a redox-dependent mechanism in lung adenocarcinoma.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Magnolin overcomes EGFR TKI resistance in NSCLC by modulation of NDRG1-NRG2-HECW1 pathway.Acta pharmacologica Sinica · 2026Article
- Isoliensinine exerts antitumor effects in lung adenocarcinoma by inhibiting APEX1-driven ROS production.Frontiers in pharmacology · 2025Article
- FTO/m6A mediates miR-138-5p maturation and regulates gefitinib resistance of lung adenocarcinoma cells by miR-138-5p/LCN2 axis.BMC cancer · 2024Article
- APE1 inhibition enhances ferroptotic cell death and contributes to hepatocellular carcinoma therapy.Cell death and differentiation · 2024Article
- Comprehensive analysis identifies DNA damage repair-related gene HCLS1 associated with good prognosis in lung adenocarcinoma.Translational cancer research · 2023Article
- Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects.Frontiers in immunology · 2023Review
- α-synucleinopathy exerts sex-dimorphic effects on the multipurpose DNA repair/redox protein APE1 in mice and humans.Progress in neurobiology · 2022Article
- APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b.Cellular and molecular life sciences : CMLS · 2022Article
- Cosuppression of NF-κB and AICDA Overcomes Acquired EGFR-TKI Resistance in Non-Small Cell Lung Cancer.Cancers · 2022Article
- Article
- APE1 shRNA-loaded cancer stem cell-derived extracellular vesicles reverse Erlotinib resistance in non-small cell lung cancer via the IL-6/STAT3 signalling.Clinical and translational medicine · 2022Article
- Claudin1 decrease induced by 1,25-dihydroxy-vitamin D3 potentiates gefitinib resistance therapy through inhibiting AKT activation-mediated cancer stem-like properties in NSCLC cells.Cell death discovery · 2022Article
- Pharmacological inhibition of Ref-1 enhances the therapeutic sensitivity of papillary thyroid carcinoma to vemurafenib.Cell death & disease · 2022Article
- Identification and validation of a novel redox-related lncRNA prognostic signature in lung adenocarcinoma.Bioengineered · 2021Article
- Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer.Cell death & disease · 2021Article
- Four long noncoding RNAs act as biomarkers in lung adenocarcinoma.Open medicine (Warsaw, Poland) · 2021Article
- Correlation of APE1 with VEGFA and CD163Oncology letters · 2020Article
- Associations between polymorphisms in genes of base excision repair pathway and lung cancer risk.Translational cancer research · 2020Article
- Identification of a long non-coding RNA signature for predicting prognosis and biomarkers in lung adenocarcinoma.Oncology letters · 2020Article
- SKA3 promotes lung adenocarcinoma metastasis through the EGFR-PI3K-Akt axis.Bioscience reports · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become the standard first-line treatment for advanced lung adenocarcinoma (LUAD) cancer patients with activating EGFR mutations. However, most patients show acquired resistance to EGFR-TKIs, thereby resulting in a modest overall survival benefit. Here, we found that expression level of APE1 was closely associated with TKI resistance in LUAD. Our clinical data show that level of APE1 was inversely correlated with progression-free survival rate and median time to progression in EGFR-mutated LUAD patients. Additionally, we observed increased expression of APE1 in TKI-resistant LUAD cell lines compared to their parental cell lines. Overexpression of APE1-protected TKI-sensitive LUAD cells from TKI-induced cell growth inhibition and cell death. In contrast, inhibition of APE1-enhanced TKI-induced apoptosis, cell growth inhibition and tumor growth inhibition in TKI-resistant LUAD. In addition, we identified that APE1 positively regulates Akt activation and APE1 overexpression-induced TKI resistance was attenuated by inhibition of Akt activity. Finally, we demonstrated that inhibition of the redox function of APE1 enhances the sensitivity of TKI-resistant LUAD cells to TKI treatment and inhibits Akt phosphorylation in TKI-resistant LUAD cells, but not by inhibition of the APE1 DNA repair function. Taken together, our data show that increased expression of APE1 significantly contributes to TKI resistance development in LUAD, and targeting APE1 may reverse acquired resistance of LUAD cells to TKI treatment. Additionally, our data show that APE1 regulates TKI resistance in LUAD cells by activating Akt signaling through a redox-dependent mechanism.
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