Universität zu Köln

Weber, Lea, Al-Refae, Klaudia, Ebbert, Juliane, Jaegers, Peter, Altmueller, Janine, Becker, Christian, Hahn, Stephan, Gisselmann, Guenter and Hatt, Hanns (2017). Activation of odorant receptor in colorectal cancer cells leads to inhibition of cell proliferation and apoptosis. PLoS One, 12 (3). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs) is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been demonstrated to have influence on cancer cell growth and progression. Here, ORs were identified using RNA-Seq analyses and RT-PCR. We demonstrated the OR protein localization in HCT116 cells using immunocytochemistry (IHC). In order to analyze the physiological role of OR51B4, we deorphanized the receptor by the use of CRE-Luciferase assays, conducted calcium imaging experiments as well as scratch-and proliferation assays. Furthermore, western blot analyses revealed the involvement of different protein kinases in the ligand-dependent signaling pathway. Receptor knockdown via shRNA was used to analyze the involvement of OR51B4. We identified OR51B4, which is highly expressed in the colon cancer cell line HCT116 and in native human colon cancer tissues. We deorphanized the receptor and identified Troenan as an effective ligand. Troenan stimulation of HCT116 cells has anti-proliferative, anti-migratory and pro-apoptotic effects, mediated by changes in the intracellular calcium level upon PLC activation. These effects cause changes in the phosphorylation levels of p38, mTor and Akt kinases. Knockdown of the receptor via shRNA confirmed the involvement of OR51B4. This study emphasizes the importance of ectopically expressed ORs in the therapy for several diseases. The findings provide the basis for alternative treatments of colorectal cancer.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Weber, Lea UNSPECIFIED UNSPECIFIED UNSPECIFIED Al-Refae, Klaudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Ebbert, Juliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaegers, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahn, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Gisselmann, Guenter UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatt, Hanns UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236743
DOI:	10.1371/journal.pone.0172491
Journal or Publication Title:	PLoS One
Volume:	12
Number:	3
Date:	2017
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-COUPLED RECEPTOR; OLFACTORY RECEPTOR; PROSTATE-CANCER; EXPRESSION; GENE; PATHWAY; FAMILY; REVEALS; MEMBERS; TARGET Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23674