ArticleCells2019
HIF-1α and HIF-2α Differently Regulate the Radiation Sensitivity of NSCLC Cells.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- Quantitative dissection of radioresistance in cancer cells: Oxygen depletion-induced biological versus chemical mechanisms and baseline mechanisms governed by HIF-1β-NRF2/TXNRD1.Neoplasia (New York, N.Y.) · 2026Article
- Normoxic HIFα-mediated metabolic rewiring in cancer as a novel therapeutic target of tumor heterogeneity.Cancer & metabolism · 2026Article
- Review
- Hypoxia-drives reversible cell cycle arrest in lung cancer cells via modulation of cellular redox and gene expression.Medical oncology (Northwood, London, England) · 2025Article
- Glucose stimulated CEST MRI pHe mapping for improved differentiation of tumors with altered hypoxia inducible factor 1alpha expression.Scientific reports · 2025Article
- CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Radioresistant mouse pheochromocytoma cell lines.Frontiers in oncology · 2025Article
- Role of HIF-1α in the Responses of Tumors to Radiotherapy and Chemotherapy.Cancer research and treatment · 2025Review
- Hypoxia A Typical Target in Human Lung Cancer Therapy.Current protein & peptide science · 2024Review
- Modern therapies of nonsmall cell lung cancer.Journal of applied genetics · 2023Review
- Type H vessel/platelet-derived growth factor receptor βCell proliferation · 2023Article
- The Underexplored Landscape of Hypoxia-Inducible Factor 2 Alpha and Potential Roles in Tumor Macrophages: A Review.Oxygen (Basel, Switzerland) · 2023Article
- Review: Mechanisms and perspective treatment of radioresistance in non-small cell lung cancer.Frontiers in immunology · 2023Review
- The role of tumor neogenesis pipelines in tumor progression and their therapeutic potential.Cancer medicine · 2023Review
- Immunometabolic interference between cancer and COVID-19.Frontiers in immunology · 2023Article
- The Role of Hypoxia-Inducible Factor Isoforms in Breast Cancer and Perspectives on Their Inhibition in Therapy.Cancers · 2022Review
- Overcoming the Impact of Hypoxia in Driving Radiotherapy Resistance in Head and Neck Squamous Cell Carcinoma.Cancers · 2022Review
- Identification of Novel Regulators of Radiosensitivity Using High-Throughput Genetic Screening.International journal of molecular sciences · 2022Review
- HIF-1α Inhibition Improves Anti-Tumor Immunity and Promotes the Efficacy of Stereotactic Ablative Radiotherapy (SABR).Cancers · 2022Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hypoxia-inducible transcription factors (HIF)-1/2α are the main oxygen sensors which regulate the adaptation to intratumoral hypoxia. The aim of this study was to assess the role of the HIF proteins in regulating the radiation response of a non-small cell lung cancer (NSCLC) in vitro model. To directly assess the unique and overlapping functions of HIF-1α and HIF-2α, we use CRISPR gene-editing to generate isogenic H1299 non-small cell lung carcinoma cells lacking HIF-1α, HIF-2α or both. We found that in HIF1 knockout cells, HIF-2α was strongly induced by hypoxia compared to wild type but the reverse was not seen in HIF2 knockout cells. Cells lacking HIF-1α were more radiation resistant than HIF2 knockout and wildtype cells upon hypoxia, which was associated with a reduced recruitment of γH2AX foci directly after irradiation and not due to differences in proliferation. Conversely, double-HIF1/2 knockout cells were most radiation sensitive and had increased γH2AX recruitment and cell cycle delay. Compensatory HIF-2α activity in HIF1 knockout cells is the main cause of this radioprotective effect. Under hypoxia, HIF1 knockout cells uniquely had a strong increase in lactate production and decrease in extracellular pH. Using genetically identical HIF-α isoform-deficient cells we identified a strong radiosensitizing of HIF1, but not of HIF2, which was associated with a reduced extracellular pH and reduced glycolysis.
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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.