ArticlePLoS biology2017
Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Repurposing BH3 mimetics to deplete tumour-infiltrating regulatory T cells and enhance anti-tumour immunity in non-small cell lung cancer.Cell death and differentiation · 2026Article
- Wnt3-mediated fibrosis and carcinogenesis of lung squamous cell carcinoma in idiopathic pulmonary fibrosis.iScience · 2026Article
- Functional Profiling of DNA Repair Pathways in Lung Cancer Patients Uncovers Radiotherapy-Induced and Cancer-Associated Alterations in Oxidative Lesion Repair.medRxiv : the preprint server for health sciences · 2026Article
- Elevated expression of ANAPC1 in lung squamous cell carcinoma: clinical implications and mechanisms.Future science OA · 2025Article
- Non-apoptotic caspase-8 is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection.Nature communications · 2025Article
- DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution.Nature genetics · 2025Article
- Enhanced radiation sensitivity, decreased DNA damage repair, and differentiation defects in airway stem cells derived from patients with chronic obstructive pulmonary disease.Stem cells translational medicine · 2024Article
- Differentiation of CD166-positive hPSC-derived lung progenitors into airway epithelial cells.Biology open · 2024Article
- Tumor Promoters and Opportunities for Molecular Cancer Prevention.Cancer discovery · 2024Review
- Rho-Associated Protein Kinase Activity Is Required for Tissue Homeostasis in theJournal of developmental biology · 2024Article
- Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Molecular and cellular basis of the dose-rate-dependent adverse effects of radiation exposure in animal models. Part II: Hematopoietic system, lung and liver.Journal of radiation research · 2023Review
- Targeting the DNA Damage Response Machinery for Lung Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Cell-intrinsic differences between human airway epithelial cells from children and adults.iScience · 2022Article
- [Lung Cancer Stem-like Cells and Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Review
- Stem Cell-derived Respiratory Epithelial Cell Cultures as Human Disease Models.American journal of respiratory cell and molecular biology · 2021Review
- Chronic lung diseases: prospects for regeneration and repair.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- NOTCH inhibition promotes bronchial stem cell renewal and epithelial barrier integrity after irradiation.Stem cells translational medicine · 2020Article
- Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells.Stem cells international · 2020Article
- The Kinome of Human Alveolar Type II and Basal Cells, and Its Reprogramming in Lung Cancer.American journal of respiratory cell and molecular biology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins and molecular processes that contribute to SqCC formation are largely unexplored. Here we show that human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor cell counterparts have limited colony-forming capacity. We demonstrate that this difference arises in part because of the ability of BSCs to repair their DNA more efficiently than alveolar cells following ionizing radiation or chemical-induced DNA damage. Analysis of mice harbouring a mutation in the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key enzyme in DNA damage repair by nonhomologous end joining (NHEJ), indicated that BSCs preferentially repair their DNA by this error-prone process. Interestingly, polyploidy, a phenomenon associated with genetically unstable cells, was only observed in the human BSC subset. Expression signature analysis indicated that BSCs are the likely cells of origin of human SqCC and that high levels of NHEJ genes in SqCC are correlated with increasing genomic instability. Hence, our results favour a model in which heavy smoking promotes proliferation of BSCs, and their predilection for error-prone NHEJ could lead to the high mutagenic burden that culminates in SqCC. Targeting DNA repair processes may therefore have a role in the prevention and therapy of SqCC.
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