Büch Thomas R H, Büch Eva A M, Boekhoff Ingrid, Steinritz Dirk, Aigner Achim
Rudolf Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Leipzig University, Haertelstrasse 16-18, D-04107 Leipzig, Germany.
Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilian University, D-80336 Munich, Germany.
Pharmaceuticals (Basel). 2018 Sep 21;11(4):90. doi: 10.3390/ph11040090.
Transient receptor potential (TRP) channels represent a large family of cation channels and many members of the TRP family have been shown to act as polymodal receptor molecules for irritative or potentially harmful substances. These chemosensory TRP channels have been extensively characterized in primary sensory and neuronal cells. However, in recent years the functional expression of these proteins in non-neuronal cells, e.g., in the epithelial lining of the respiratory tract has been confirmed. Notably, these proteins have also been described in a number of cancer types. As sensor molecules for noxious compounds, chemosensory TRP channels are involved in cell defense mechanisms and influence cell survival following exposure to toxic substances via the modulation of apoptotic signaling. Of note, a number of cytostatic drugs or drug metabolites can activate these TRP channels, which could affect the therapeutic efficacy of these cytostatics. Moreover, toxic inhalational substances with potential involvement in lung carcinogenesis are well established TRP activators. In this review, we present a synopsis of data on the expression of chemosensory TRP channels in lung cancer cells and describe TRP agonists and TRP-dependent signaling pathways with potential relevance to tumor biology. Furthermore, we discuss a possible role of TRP channels in the non-genomic, tumor-promoting effects of inhalational carcinogens such as cigarette smoke.
瞬时受体电位（TRP）通道是一大类阳离子通道，TRP家族的许多成员已被证明可作为刺激性或潜在有害物质的多模式受体分子。这些化学感应性TRP通道已在初级感觉细胞和神经元细胞中得到广泛表征。然而，近年来已证实这些蛋白质在非神经元细胞（如呼吸道上皮衬里）中具有功能性表达。值得注意的是，这些蛋白质在多种癌症类型中也有描述。作为有害化合物的传感分子，化学感应性TRP通道参与细胞防御机制，并通过调节凋亡信号影响细胞在接触有毒物质后的存活。值得注意的是，一些细胞毒性药物或药物代谢产物可激活这些TRP通道，这可能会影响这些细胞毒性药物的治疗效果。此外，与肺癌发生潜在相关的有毒吸入物质是公认的TRP激活剂。在本综述中，我们概述了肺癌细胞中化学感应性TRP通道表达的数据，并描述了与肿瘤生物学潜在相关的TRP激动剂和TRP依赖性信号通路。此外，我们讨论了TRP通道在吸入性致癌物（如香烟烟雾）的非基因组、促肿瘤作用中的可能作用。
