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Ulke, H.M. ; Mutze, K. ; Lehmann, M. ; Wagner, D.E. ; Heinzelmann, K. ; Guenther, A.* ; Eickelberg, O.* ; Königshoff, M.

The oncogene ECT2 contributes to a hyperplastic, proliferative lung epithelial cell phenotype in idiopathic pulmonary fibrosis.

Am. J. Respir. Cell Mol. Biol. 61, 713-726 (2019)
Verlagsversion DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Idiopathic pulmonary fibrosis (IPF) and lung cancer are progressive lung diseases with a poor prognosis. IPF is a risk factor for the development of lung cancer, and the incidence of lung cancer is increased in patients with IPF. The disease pathogenesis of IPF and lung cancer involves common genetic alterations, dysregulated pathways, and the emergence of hyperplastic and metaplastic epithelial cells. Here, we aimed to identify novel, common mediators that might contribute to epithelial cell reprogramming in IPF. Gene set enrichment analysis of publicly available non-small cell lung cancer and IPF datasets revealed a common pattern of misregulated genes linked to cell proliferation and transformation. The oncogene ECT2 (epithelial cell transforming sequence 2), a guanine nucleotide exchange factor for Rho GTPases, was highly enriched in both IPF and non-small cell lung cancer compared with nondiseased controls. Increased expression of ECT2 was verified by qPCR and Western blotting in bleomycin-induced lung fibrosis and human IPF tissue. Immunohistochemistry demonstrated strong expression of ECT2 staining in hyperplastic alveolar epithelial type II (ATII) cells in IPF, as well as its colocalization with proliferating cell nuclear antigen, a well-known proliferation marker. Increased ECT2 expression coincided with enhanced proliferation of primary mouse ATII cells as analyzed by flow cytometry. ECT2 knockdown in ATII cells resulted in decreased proliferation and collagen I expression in vitro. These data suggest that the oncogene ECT2 contributes to epithelial cell reprogramming in IPF, and further emphasize the hyperplastic, proliferative ATII cell as a potential target in patients with IPF and lung cancer.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Alveolar Epithelial Cells ; Oncogenic Pathways ; Lung Fibrosis ; Gene Set Enrichment Analysis ; Lung Cancer; Mesenchymal Transition; Cancer; Expression; Survival; Overexpression; Prevalence; Mechanisms; Nintedanib; Impact
ISSN (print) / ISBN 1044-1549
e-ISSN 1535-4989
Zeitschrift American Journal of Respiratory Cell and Molecular Biology
Quellenangaben Band: 61, Heft: 6, Seiten: 713-726 Artikelnummer: , Supplement: ,
Verlag American Thoracic Society
Verlagsort 25 Broadway, 18 Fl, New York, Ny 10004 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Lung Repair and Regeneration (LRR)