Format

Send to

Choose Destination
Sci Rep. 2017 Aug 31;7(1):10292. doi: 10.1038/s41598-017-09554-x.

LSD1 modulates the non-canonical integrin β3 signaling pathway in non-small cell lung carcinoma cells.

Author information

1
Institute of Pathology, University Hospital of Cologne, 50931, Cologne, Germany. so-young.lim@uk-koeln.de.
2
The Center for Molecular Medicine Cologne (CMMC), 50931, Cologne, Germany. so-young.lim@uk-koeln.de.
3
Institute of Pathology, University Hospital of Cologne, 50931, Cologne, Germany.
4
The Center for Molecular Medicine Cologne (CMMC), 50931, Cologne, Germany.
5
Center of Integrative Oncology, University Clinic of Cologne and Bonn, 50937, Cologne, Germany.
6
Functional Epigenomics, University of Cologne, 50931, Cologne, Germany.
7
Department of Translational Genomics, Medical Faculty, University of Cologne, 50931, Cologne, Germany.
8
Centre Léon Bérard, 69008, Lyon, France.
9
Lung Cancer Group Cologne, University Hospital of Cologne, 50937, Cologne, Germany.
10
Clinic for Internal Medicine, University Hospital of Cologne, 50937, Cologne, Germany.
11
Max Planck Institute for Molecular Genetics, 14195, Berlin, Germany.
12
German Cancer Research Center, German Cancer Consortium (DKTK), 69120, Heidelberg, Germany.

Abstract

The epigenetic writer lysine-specific demethylase 1 (LSD1) is aberrantly upregulated in many cancer types and its overexpression correlates with poor survival and tumor progression. In this study, we analysed LSD1 function in non-small cell lung cancer adenocarcinomas. Expression profiling of 182 cases of lung adenocarcinoma proved a significant correlation of LSD1 overexpression with lung adenocarcinoma progression and metastasis. KRAS-mutated lung cancer cell clones were stably silenced for LSD1 expression. RNA-seq and comprehensive pathway analysis revealed, that genes related to a recently described non-canonical integrin β3 pathway, were significantly downregulated by LSD1 silencing. Hence, invasion and self-renewal capabilities were strongly decreased. Notably, this novel defined LSD1/integrin β3 axis, was also detected in human lung adenocarcinoma specimens. Furthermore, the linkage of LSD1 to an altered expression pattern of lung-lineage specific transcription factors and genes, which are involved in alveolar epithelial differentiation, was demonstrated. Thus, our findings point to a LSD1-integrin β3 axis, conferring attributes of invasiveness and tumor progression to lung adenocarcinoma.

PMID:
28860622
PMCID:
PMC5578970
DOI:
10.1038/s41598-017-09554-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center