ArticleProceedings of the National Academy of Sciences of the United States of America2016
Ablation of Liver X receptors α and β leads to spontaneous peripheral squamous cell lung cancer in mice.
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. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Pooled it
- Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis.Journal of advanced research · 2025Article
- SREBP-2 promotes cancer progression through the mevalonate-Akt pathway in non-small cell lung cancer.Scientific reports · 2025Article
- The role of estrogen receptor β in maintaining basal cells and modulating the immune environment in the prostate.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Alveolar macrophages: guardians of the alveolar lipid galaxy.Current opinion in lipidology · 2025Review
- Unravelling the role of tumor microenvironment responsive nanobiomaterials in spatiotemporal controlled drug delivery for lung cancer therapy.Drug delivery and translational research · 2025Review
- Lipid-Laden Macrophages in Pulmonary Diseases.Cells · 2024Review
- The role of cholesterol metabolism in lung cancer.Oncology research · 2024Review
- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Loss of ERβ in Aging LXRαβ Knockout Mice Leads to Colitis.International journal of molecular sciences · 2023Article
- Emerging Insights into Liver X Receptor α in the Tumorigenesis and Therapeutics of Human Cancers.Biomolecules · 2023Review
- Liver X receptors and estrogen receptor β, two players in a rare subtype of NSCLC.International journal of biological sciences · 2023Article
- Cholesterol-Lowering Phytochemicals: Targeting the Mevalonate Pathway for Anticancer Interventions.Frontiers in genetics · 2022Review
- Integrated Analysis Highlights the Immunosuppressive Role of TREM2Frontiers in immunology · 2022Article
- Article
- Understanding the Co-Epidemic of Obesity and COVID-19: Current Evidence, Comparison with Previous Epidemics, Mechanisms, and Preventive and Therapeutic Perspectives.Current obesity reports · 2021Review
- When Two Pandemics Meet: Why Is Obesity Associated with Increased COVID-19 Mortality?Med (New York, N.Y.) · 2020Review
- A conserved role for AMP-activated protein kinase in NGLY1 deficiency.PLoS genetics · 2020Article
- Understanding the molecular association between hyperkalemia and lung squamous cell carcinomas.BMC medical genetics · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
The etiology of peripheral squamous cell lung cancer (PSCCa) remains unknown. Here, we show that this condition spontaneously develops in mice in which the genes for two oxysterol receptors, Liver X Receptor (LXR) α (Nr1h3) and β (Nr1h2), are inactivated. By 1 y of age, most of these mice have to be euthanized because of severe dyspnea. Starting at 3 mo, the lungs of LXRα,β(Dko) mice, but not of LXRα or LXRβ single knockout mice, progressively accumulate foam cells, so that by 1 y, the lungs are covered by a "golden coat." There is infiltration of inflammatory cells and progressive accumulation of lipid in the alveolar wall, type 2 pneumocytes, and macrophages. By 14 mo, there are three histological lesions: one resembling adenomatous hyperplasia, one squamous metaplasia, and one squamous cell carcinoma characterized by expression of transformation-related protein (p63), sex determining region Y-box 2 (Sox2), cytokeratin 14 (CK14), and cytokeratin 13 (CK13) and absence of thyroid transcription factor 1 (TTF1), and prosurfactant protein C (pro-SPC). RNA sequencing analysis at 12 mo confirmed a massive increase in markers of M1 macrophages and lymphocytes. The data suggest a previously unidentified etiology of PSCCa: cholesterol dysregulation and M1 macrophage-predominant lung inflammation combined with damage to, and aberrant repair of, lung tissue, particularly the peripheral parenchyma. The results raise the possibility that components of the LXR signaling may be useful targets in the treatment of PSCCa.
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Registered trials
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