The Oncogene ECT2 Contributes to a Hyperplastic, Proliferative Lung Epithelial Cell Phenotype in Idiopathic Pulmonary Fibrosis

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title = "The Oncogene ECT2 Contributes to a Hyperplastic, Proliferative Lung Epithelial Cell Phenotype in Idiopathic Pulmonary Fibrosis",
abstract = "Idiopathic pulmonary fibrosis (IPF) and lung cancer represent progressive lung diseases with a poor prognosis. IPF represents a risk factor for the development of lung cancer, and the incidence of lung cancer is increased in patients with IPF. 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 (GSEA) of publicly available non-small cell lung cancer (NSCLC) and IPF datasets revealed a common pattern of misregulated genes, linked to cell proliferation and transformation. The oncogene epithelial cell transforming sequence 2 (ECT2), a guanine nucleotide exchange factor (GEF) for Rho GTPases, was highly enriched in both, IPF and NSCLC, compared to non-diseased 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 type II alveolar epithelial (ATII) cells in IPF, as well as its colocalization with PCNA, a well-known proliferation marker. Increased ECT2 expression coincided with enhanced proliferation of primary mouse ATII cells as analyzed by flow cytometric analysis. 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 underline the hyperplastic, proliferative ATII cell as a potential target in patients with IPF and lung cancer.",
keywords = "alveolar epithelial cells, gene set enrichment analysis, lung cancer, lung fibrosis, oncogenic pathways",
author = "Ulke, {Henrik M} and Kathrin Mutze and Mareike Lehmann and Wagner, {Darcy E} and Katharina Heinzelmann and Andreas G{\"u}nther and Oliver Eickelberg and Melanie K{\"o}nigshoff",
year = "2019",
month = "12",
day = "1",
doi = "10.1165/rcmb.2019-0047OC",
language = "English",
volume = "61",
pages = "713--726",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1535-4989",
publisher = "American Thoracic Society",
number = "6",