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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

So-Young Lim, Iris Macheleidt, Priya Dalvi, Stephan C. Schäfer, Martin Kerick, Luka Ozretić, Sandra Ortiz-Cuaran, Julie George, Sabine Merkelbach-Bruse, Jürgen Wolf, Bernd Timmermann, Roman K. Thomas, Michal R. Schweiger, Reinhard Buettner, Margarete Odenthal

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. More... »

PAGES

10292

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-09554-x

DOI

http://dx.doi.org/10.1038/s41598-017-09554-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091356630

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28860622


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