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Spella, M.* ; Lilis, I.* ; Pepe, M. ; Chen, Y.* ; Armaka, M.* ; Lamort, A.-S. ; Zazara, D.E.* ; Roumelioti, F.* ; Vreka, M. ; Kanellakis, N.I.* ; Wagner, D.E. ; Giannou, A.D.* ; Armenis, V.* ; Arendt, K.A.M. ; Klotz, L.V. ; Toumpanakis, D.* ; Karavana, V.* ; Zakynthinos, S.G.* ; Giopanou, I.* ; Marazioti, A.* ; Aidinis, V.* ; Sotillo, R.* ; Stathopoulos, G.T.

Club cells form lung adenocarcinomas and maintain the alveoli of adult mice.

eLife 8:e45571 (2019)
Publ. Version/Full Text Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Lung cancer and chronic lung diseases impose major disease burdens worldwide and are caused by inhaled noxious agents including tobacco smoke. The cellular origins of environmental-induced lung tumors and of the dysfunctional airway and alveolar epithelial turnover observed with chronic lung diseases are unknown. To address this, we combined mouse models of genetic labeling and ablation of airway (club) and alveolar cells with exposure to environmental noxious and carcinogenic agents. Club cells are shown to survive KRAS mutations and to form lung tumors after tobacco carcinogen exposure. Increasing numbers of club cells are found in the alveoli with aging and after lung injury, but go undetected since they express alveolar proteins. Ablation of club cells prevents chemical lung tumors and causes alveolar destruction in adult mice. Hence club cells are important in alveolar maintenance and carcinogenesis and may be a therapeutic target against premalignancy and chronic lung disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Airway Transcriptome ; Cancer Biology ; Cell Biology ; Chemical Carcinogenesis ; Human ; Lung Adenocarcinoma ; Mouse ; Urethane; Stem-cells; Cancer; Gene; Identification; Expression; Origin; Mouse; Contributes; Progenitor; Epithelium
Language
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Journal eLife
Quellenangaben Volume: 8, Issue: , Pages: , Article Number: e45571 Supplement: ,
Publisher eLife Sciences Publications
Publishing Place Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Lung Research
PSP Element(s) G-501600-003
G-503100-001
DOI 10.7554/eLife.45571
WOS ID WOS:000473590100001
Scopus ID 85069265418
PubMed ID 31140976
Erfassungsdatum 2019-06-04
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