ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2021
Lung Cancer Models Reveal Severe Acute Respiratory Syndrome Coronavirus 2-Induced Epithelial-to-Mesenchymal Transition Contributes to Coronavirus Disease 2019 Pathophysiology.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- DNA methylation predicts the outcome of COVID-19 patients with acute respiratory distress syndrome.Journal of translational medicine · 2022Trial
- Skin Basal Cell Carcinosarcoma in a Trichoblastic Guise-Molecular Characterization of a Novel Entity Mimicking a Pyoderma Gangrenosum.Dermatopathology (Basel, Switzerland) · 2026Article
- Supplementation of αKG along with TGFβ/HIF1α antagonist rescues lung fibrosis in mice with severe SARS-CoV-2 infection.Journal of translational medicine · 2026Article
- SARS-CoV2 and Anti-COVID-19 mRNA Vaccines: Is There a Plausible Mechanistic Link with Cancer?Cancers · 2025Review
- Targeted Therapies Modulating Mesenchymal-Epithelial Transition-Linked Oncogenic Signaling in the Tumor Microenvironment: Comparative Profiling of Capmatinib, Bemcentinib, and Galunisertib.Journal of clinical medicine · 2025Review
- Advanced Animal Replacement Testing Strategies Using Stem Cell and Organoids.International journal of stem cells · 2025Review
- Role of the Neanderthal Genome in Genetic Susceptibility to COVID-19: 3p21.31 Locus in the Spotlight.Biochemical genetics · 2024Review
- The role of epithelial-mesenchymal transition in pulmonary fibrosis: lessons from idiopathic pulmonary fibrosis and COVID-19.Cell communication and signaling : CCS · 2024Review
- Risk of COVID-19 infection in patients with NSCLC receiving EGFR-TKI targeted therapy during the first wave in China.The Journal of international medical research · 2024Article
- The association of rs17713054 with Neanderthal origin at 3p21.31 locus with the severity of COVID-19 in Iranian patients.Scientific reports · 2024Article
- FOT Technique Applied for Monitoring of COVID-19 Pneumonia Reveals Small Airways Involvement.Diagnostics (Basel, Switzerland) · 2024Article
- Age-specific nasal epithelial responses to SARS-CoV-2 infection.Nature microbiology · 2024Article
- Dark under the Lamp: Neglected Biological Pollutants in the Environment Are Closely Linked to Lung Cancer.International journal of molecular sciences · 2024Review
- Review
- Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health.Annual review of physiology · 2024Review
- Respiratory Syncytial Virus Infection Does Not Induce Epithelial-Mesenchymal Transition.Journal of virology · 2023Article
- Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms.Vaccines · 2023Review
- Cancer Patients during COVID-19 Pandemic: A Mini-Review.Healthcare (Basel, Switzerland) · 2023Review
- Gas6/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients.International journal of molecular sciences · 2023Review
- Genetic Associations with Coronavirus Susceptibility and Disease Severity.Advances in experimental medicine and biology · 2023Review
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Authors and funding
28 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionCoronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which enters host cells through the cell surface proteins ACE2 and TMPRSS2.
methodsUsing a variety of normal and malignant models and tissues from the aerodigestive and respiratory tracts, we investigated the expression and regulation of ACE2 and TMPRSS2.
resultsWe find that ACE2 expression is restricted to a select population of epithelial cells. Notably, infection with SARS-CoV-2 in cancer cell lines, bronchial organoids, and patient nasal epithelium induces metabolic and transcriptional changes consistent with epithelial-to-mesenchymal transition (EMT), including up-regulation of ZEB1 and AXL, resulting in an increased EMT score. In addition, a transcriptional loss of genes associated with tight junction function occurs with SARS-CoV-2 infection. The SARS-CoV-2 receptor, ACE2, is repressed by EMT through the transforming growth factor-β, ZEB1 overexpression, and onset of EGFR tyrosine kinase inhibitor resistance. This suggests a novel model of SARS-CoV-2 pathogenesis in which infected cells shift toward an increasingly mesenchymal state, associated with a loss of tight junction components with acute respiratory distress syndrome-protective effects. AXL inhibition and ZEB1 reduction, as with bemcentinib, offer a potential strategy to reverse this effect.
conclusionsThese observations highlight the use of aerodigestive and, especially, lung cancer model systems in exploring the pathogenesis of SARS-CoV-2 and other respiratory viruses and offer important insights into the potential mechanisms underlying the morbidity and mortality of coronavirus disease 2019 in healthy patients and patients with cancer alike.
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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.