ArticleMolecular cancer research : MCR2018
Hypoxia Promotes Resistance to EGFR Inhibition in NSCLC Cells via the Histone Demethylases, LSD1 and PLU-1.
Article in Molecular cancer research : MCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 66 citations in OpenAlex.
- Roles of KDM5 demethylases in therapeutic resistance of cancers.Epigenetics & chromatin · 2025Review
- GPR81 nuclear transportation is critical for cancer growth and progression in lung and other solid cancers.World journal of clinical oncology · 2025Article
- KDM1A/LSD1 inhibition enhances chemotherapy response in ovarian cancer.Molecular carcinogenesis · 2024Article
- The role of histone post-translational modifications in cancer and cancer immunity: functions, mechanisms and therapeutic implications.Frontiers in immunology · 2024Review
- Dysregulated Signalling Pathways Driving Anticancer Drug Resistance.International journal of molecular sciences · 2023Review
- Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double-strand break repair and augments the efficacy of temozolomide in glioblastoma.Neuro-oncology · 2023Article
- Targeting epigenetic regulators to overcome drug resistance in cancers.Signal transduction and targeted therapy · 2023Review
- LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials.Frontiers in pharmacology · 2023Review
- Identification of Master Regulators Driving Disease Progression, Relapse, and Drug Resistance in Lung Adenocarcinoma.Frontiers in bioinformatics · 2022Article
- TdIF1-LSD1 Axis Regulates Epithelial-Mesenchymal Transition and Metastasis via Histone Demethylation of E-Cadherin Promoter in Lung Cancer.International journal of molecular sciences · 2021Article
- Identification of Prognostic Gene Biomarkers in Non-Small Cell Lung Cancer Progression by Integrated Bioinformatics Analysis.Biology · 2021Article
- [Research Progress of Epigenetic Mechanism in Acquired Resistance of Targeted Therapy in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- Review
- Article
- Hypoxia-induced Tie1 drives stemness and cisplatin resistance in non-small cell lung carcinoma cells.Cancer cell international · 2021Article
- Overexpression of CTEN is associated with gefitinib resistance in non-small cell lung cancer.Oncology letters · 2021Article
- SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Review
- Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway.Cancer research · 2020Article
- Review
- Epigenetic basis of cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
The development of small-molecule tyrosine kinase inhibitors (TKI) specific for epidermal growth factor receptors (EGFR) with activating mutations has led to a new paradigm in the treatment of non-small cell lung cancer (NSCLC) patients. However, most patients eventually develop resistance. Hypoxia is a key microenvironmental stress in solid tumors that is associated with poor prognosis due, in part, to acquired resistance to conventional therapy. This study documents that long-term, moderate hypoxia promotes resistance to the EGFR TKI, gefitinib, in the NSCLC cell line HCC827, which harbors an activating EGFR mutation. Following hypoxic growth conditions, HCC827 cells treated with gefitinib upregulated N-cadherin, fibronectin, and vimentin expression and downregulated E-cadherin, characteristic of an epithelial-mesenchymal transition (EMT), which prior studies have linked to EGFR TKI resistance. Mechanistically, knockdown of the histone demethylases, LSD1 and PLU-1, prevented and reversed hypoxia-induced gefitinib resistance, with inhibition of the associated EMT, suggesting that LSD1 and PLU-1 play key roles in hypoxia-induced gefitinib resistance and EMT. Moreover, hypoxia-treated HCC827 cells demonstrated more aggressive tumor growth
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Registered trials
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.