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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)
Verlagsversion 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Airway Transcriptome ; Cancer Biology ; Cell Biology ; Chemical Carcinogenesis ; Human ; Lung Adenocarcinoma ; Mouse ; Urethane; Stem-cells; Cancer; Gene; Identification; Expression; Origin; Mouse; Contributes; Progenitor; Epithelium
Sprache
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Zeitschrift eLife
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: e45571 Supplement: ,
Verlag eLife Sciences Publications
Verlagsort Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Lung Research
PSP-Element(e) 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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