Lim, So-Young, Macheleidt, Iris, Dalvi, Priya, Schaefer, Stephan C., Kerick, Martin ORCID: 0000-0002-6298-4514, Ozretic, Luka, Ortiz-Cuaran, Sandra, George, Julie, Merkelbach-Bruse, Sabine, Wolf, Juergen, Timmermann, Bernd, Thomas, Roman K., Schweiger, Michal R., Buettner, Reinhard and Odenthal, Margarete (2017). LSD1 modulates the non-canonical integrin beta 3 signaling pathway in non-small cell lung carcinoma cells. Sci Rep, 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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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 beta 3 pathway, were significantly downregulated by LSD1 silencing. Hence, invasion and self-renewal capabilities were strongly decreased. Notably, this novel defined LSD1/integrin beta 3 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 beta 3 axis, conferring attributes of invasiveness and tumor progression to lung adenocarcinoma.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lim, So-YoungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macheleidt, IrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dalvi, PriyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, Stephan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerick, MartinUNSPECIFIEDorcid.org/0000-0002-6298-4514UNSPECIFIED
Ozretic, LukaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortiz-Cuaran, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merkelbach-Bruse, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timmermann, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schweiger, Michal R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, MargareteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-221348
DOI: 10.1038/s41598-017-09554-x
Journal or Publication Title: Sci Rep
Volume: 7
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EXPRESSION ANALYSIS; STEM-CELLS; CANCER; ADENOCARCINOMA; ALPHA-6-BETA-4; MORPHOGENESIS; PROGRESSION; POPULATION; PROGENITOR; RENEWALMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22134

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