ArticleProceedings of the National Academy of Sciences of the United States of America2010
HIF-2alpha deletion promotes Kras-driven lung tumor development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses that pooled it.
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Who cites it
85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- A regulation probability model-based meta-analysis of multiple transcriptomics data sets for cancer biomarker identification.BMC bioinformatics · 2017Pooled it
- Prognostic value and clinicopathological differences of HIFs in colorectal cancer: evidence from meta-analysis.PloS one · 2013Pooled it
- Normoxic HIFα-mediated metabolic rewiring in cancer as a novel therapeutic target of tumor heterogeneity.Cancer & metabolism · 2026Article
- Activating KRAS mutations mark premalignant cystic structures in congenital pulmonary airway malformations.Respiratory research · 2026Article
- HIF2α negatively regulates MYCN protein levels and promotes a low-risk noradrenergic phenotype in neuroblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comprehensive analysis of disulfidoptosis-related genes reveals molecular heterogeneity and key regulators in retinoblastoma progression.Translational pediatrics · 2025Article
- Mechanistic Insights into Tumorigenesis from Serum Proteins.medRxiv : the preprint server for health sciences · 2025Article
- Single-cell analysis of lung epithelial cells reveals age and cell population-specific responses to SARS-CoV-2 infection in ciliated cells.Clinical and experimental immunology · 2025Article
- Review
- Identification of prognostic biomarkers of smoking-related lung cancer.Journal of thoracic disease · 2024Article
- EPAS1/HIF-2α Acts as an Unanticipated Tumor-Suppressive Role in Papillary Thyroid Carcinoma.International journal of general medicine · 2023Article
- Evaluation of AMG510 Therapy onBioengineering (Basel, Switzerland) · 2022Article
- Obstructive sleep apnea and the incidence and mortality of gastrointestinal cancers: a systematic review and meta-analysis of 5,120,837 participants.Journal of gastrointestinal oncology · 2022Article
- Hypoxia signaling: Challenges and opportunities for cancer therapy.Seminars in cancer biology · 2022Review
- The Proteomic Profile of Interstitial Lung Abnormalities.American journal of respiratory and critical care medicine · 2022Article
- Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy.Cancers · 2022Review
- Article
- Hypoxia-Inducible Factors in Cancer.Cancer research · 2022Article
- Aberrant expression of HIF3A in plasma of patients with non-small cell lung cancer and its clinical significance.Journal of clinical laboratory analysis · 2021Article
- Multi-omics analysis reveals contextual tumor suppressive and oncogenic gene modules within the acute hypoxic response.Nature communications · 2021Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. The oxygen-sensitive hypoxia inducible factor (HIF) transcriptional regulators HIF-1alpha and HIF-2alpha are overexpressed in many human NSCLCs, and constitutive HIF-2alpha activity can promote murine lung tumor progression, suggesting that HIF proteins may be effective NSCLC therapeutic targets. To investigate the consequences of inhibiting HIF activity in lung cancers, we deleted Hif-1alpha or Hif-2alpha in an established Kras(G12D)-driven murine NSCLC model. Deletion of Hif-1alpha had no obvious effect on tumor growth, whereas Hif-2alpha deletion resulted in an unexpected increase in tumor burden that correlated with reduced expression of the candidate tumor suppressor gene Scgb3a1 (HIN-1). Here, we identify Scgb3a1 as a direct HIF-2alpha target gene and demonstrate that HIF-2alpha regulates Scgb3a1 expression and tumor formation in human Kras(G12D)-driven NSCLC cells. AKT pathway activity, reported to be repressed by Scgb3a1, was enhanced in HIF-2alpha-deficient human NSCLC cells and xenografts. Finally, a direct correlation between HIF-2alpha and SCGB3a1 expression was observed in approximately 70% of human NSCLC samples analyzed. These data suggest that, whereas HIF-2alpha overexpression can contribute to NSCLC progression, therapeutic inhibition of HIF-2alpha below a critical threshold may paradoxically promote tumor growth by reducing expression of tumor suppressor genes, including Scgb3a1.
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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.