ArticleAmerican journal of respiratory and critical care medicine2017
SOX2 Drives Bronchial Dysplasia in a Novel Organotypic Model of Early Human Squamous Lung Cancer.
Article in American journal of respiratory and critical care medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Utilising multi-modal data-driven network analysis to identify monotherapy and combinational therapy targets in SOX2-dependent squamous cell lung cancer.Communications chemistry · 2025Article
- A human model to deconvolve genotype-phenotype causations in lung squamous cell carcinoma.Nature communications · 2025Article
- Defining precancer: a grand challenge for the cancer community.Nature reviews. Cancer · 2024Review
- Chronic lung inflammation and CK14+ basal cell proliferation induce persistent alveolar-bronchiolization in SARS-CoV-2-infected hamsters.EBioMedicine · 2024Article
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- Cell Cultures at the Air-Liquid Interface and Their Application in Cancer Research.Methods in molecular biology (Clifton, N.J.) · 2023Article
- LncRNA PCAT1 activates SOX2 and suppresses radioimmune responses via regulating cGAS/STING signalling in non-small cell lung cancer.Clinical and translational medicine · 2022Article
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- Mapping lung squamous cell carcinoma pathogenesis through in vitro and in vivo models.Communications biology · 2021Review
- Air-liquid interface cultures of the healthy and diseased human respiratory tract: promises, challenges and future directions.Advanced nanobiomed research · 2021Article
- Progress towards non-small-cell lung cancer models that represent clinical evolutionary trajectories.Open biology · 2021Review
- Novel prognostic molecular markers in lung cancer.Oncology letters · 2020Review
- Integrative analysis of DNA methylation-driven genes for the prognosis of lung squamous cell carcinoma using MethylMix.International journal of medical sciences · 2020Article
- Acquisition of Cancer Stem Cell-like Properties in Human Small Airway Epithelial Cells after a Long-term Exposure to Carbon Nanomaterials.Environmental science. Nano · 2019Article
- Cancer-associated fibroblasts suppress SOX2-induced dysplasia in a lung squamous cancer coculture.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Diagnostic Value of Multi-Slice Spiral Computed Tomography for Bronchial Dysplasia in Premature Infants.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Successful Establishment of Primary Type II Alveolar Epithelium with 3D Organotypic Coculture.American journal of respiratory cell and molecular biology · 2018Article
- Knockdown of long non-coding RNA NEAT1 inhibits glioma cell migration and invasion via modulation of SOX2 targeted by miR-132.Molecular cancer · 2018Article
- FGFR2 is required for airway basal cell self-renewal and terminal differentiation.Development (Cambridge, England) · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
rationaleImproving the early detection and chemoprevention of lung cancer are key to improving outcomes. The pathobiology of early squamous lung cancer is poorly understood. We have shown that amplification of sex-determining region Y-box 2 (SOX2) is an early and consistent event in the pathogenesis of this disease, but its functional oncogenic potential remains uncertain. We tested the impact of deregulated SOX2 expression in a novel organotypic system that recreates the molecular and microenvironmental context in which squamous carcinogenesis occurs.
objectives(1) To develop an in vitro model of bronchial dysplasia that recapitulates key molecular and phenotypic characteristics of the human disease; (2) to test the hypothesis that SOX2 deregulation is a key early event in the pathogenesis of bronchial dysplasia; and (3) to use the model for studies on pathogenesis and chemoprevention.
methodsWe engineered the inducible activation of oncogenes in immortalized bronchial epithelial cells. We used three-dimensional tissue culture to build an organotypic model of bronchial dysplasia. MEASUREMENTS AND MAIN
resultsWe recapitulated human bronchial dysplasia in vitro. SOX2 deregulation drives dysplasia, and loss of tumor promoter 53 is a cooperating genetic event that potentiates the dysplastic phenotype. Deregulated SOX2 alters critical genes implicated in hallmarks of cancer progression. Targeted inhibition of AKT prevents the initiation of the dysplastic phenotype.
conclusionsIn the appropriate genetic and microenvironmental context, acute deregulation of SOX2 drives bronchial dysplasia. This confirms its oncogenic potential in human cells and affords novel insights into the impact of SOX2 deregulation. This model can be used to test therapeutic agents aimed at chemoprevention.
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