Helional-induced activation of human olfactory receptor 2J3 promotes apoptosis and inhibits proliferation in a non-small-cell lung cancer cell line
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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DOI：
10.1016/j.ejcb.2016.11.004
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发表时间：
2017-01-01
影响因子：
6.6
通讯作者：
Hatt, Hanns
中科院分区：
文献类型：
--
作者：
Kalbe, Benjamin;Schulz, Viola Maria;Hatt, Hanns
过去十年的研究已经将嗅觉受体（OR）的功能表达定位于嗅觉上皮细胞之外的细胞。在人类肝癌和前列腺癌细胞中，气味激活 OR 会调节基本生理过程，并对增殖产生抑制作用。呼吸道细胞与周围空气直接接触，其中存在大量挥发性分子，尤其是气味。非小细胞肺癌（NSCLC）患病率高、死亡率高且治疗难度大。非小细胞肺癌细胞对常见的化疗方法几乎有抵抗力，手术切除是大多数患者治愈的唯一可能机会。治疗 NSCLC 的新方法是当前许多研究的焦点。因此，表征肺部癌细胞中 OR 的功能表达并研究 OR 对病理生理过程的影响是很有意义的。在本研究中，我们证明了 NSCLC 细胞系 A549 中 OR2J3 和胞质 Ca2+ 的表达通过激活激动剂 helional 增加。我们进一步研究了潜在的途径。 Helional 触发磷酸肌醇 1-3 激酶 (PI3K)，发出细胞内 Ca2+ 释放和 ERK 磷酸化的信号。我们在 helional 的长期刺激实验中观察到 OR2J3 激活会诱导细胞凋亡并抑制细胞增殖和迁移。我们的研究提供了 NSCLC 细胞中 OR 的功能表达及其假定的治疗影响的第一个证据。 (C) 2016 爱思唯尔有限公司。版权所有。
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 phoshoinosito1-3 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. (C) 2016 Elsevier GmbH. All rights reserved.