Helional-induced activation of human olfactory receptor 2J3 promotes apoptosis and inhibits proliferation in a non-small-cell lung cancer cell line

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• 作者：Benjamin Kalbe^a ; ^{benjamin.kalbe@rub.de} ; Viola Maria Schulz^a ; Marian Schlimm^a ; Stathis Philippou^b ; Nikolina Jovancevic^a ; Fabian Jansen^a ; Paul Scholz^a ; Hermann Lü ; bbert^c ; Marvin Jarocki^d ; Andreas Faissner^d ; Erich Hecker^e ; Sophie Veitinger^a ; Teresa Tsai^a ; Sabrina Osterloh^a ; Hanns Hatt^a
• 关键词：Olfactory receptor ; GPCR ; NSCLC ; Signaling ; Cell physiology ; Apoptosis
• 刊名：European Journal of Cell Biology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：96
• 期：1
• 页码：34-46
• 全文大小：5819 K
• 卷排序：96

文摘

Studies within the last decade have localized the functional expression of olfactory receptors (ORs) to cells outside of the olfactory epithelium. In human hepatocarcinoma and prostate cancer cells, the activation of ORs by odors modulates elementary physiological processes and leads to an inhibitory effect on proliferation. Cells of the respiratory tract are in direct contact with the surrounding air, in which a myriad of volatile molecules, especially odors, are present. Non-small-cell lung cancer (NSCLC) has a high prevalence, a high mortality rate and is difficult to treat. NSCLC cells are nearly resistant to common chemotherapeutic approaches, and surgical resection provides the only possible chance of a cure for most patients. New approaches for the treatment of NSCLC are the focus of many current studies. Thus, it is of interest to characterize the functional expression of ORs in cancer cells of the lung and to investigate the impact of ORs on pathophysiological processes. In the present study, we demonstrate that the expression of OR2J3 and cytosolic Ca2+ increase via the activation of the agonist helional in the NSCLC cell line A549. We further investigated the underlying pathway. Helional triggers phoshoinositol-3 kinase (PI3K), signaling the release of intracellular Ca2+ and phosphorylation of ERK. We observed that OR2J3 activation induces apoptosis and inhibits cell proliferation and migration in long-term stimulus experiments with helional. Our study provides the first evidence of the functional expression of an OR in NSCLC cells and its putative therapeutic impact.