Fels Benedikt, Bulk Etmar, Pethő Zoltán, Schwab Albrecht
Institut für Physiologie II, Robert-Koch-Str. 27b, 48149 Münster, Germany.
Pharmaceuticals (Basel). 2018 May 17;11(2):48. doi: 10.3390/ph11020048.
A dysregulated cellular Ca homeostasis is involved in multiple pathologies including cancer. Changes in Ca signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby "re-program" and "misuse" the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues. Hence, ion channels and transporters are key modulators of cancer progression. This review focuses on the role of transient receptor potential (TRP) channels in the metastatic cascade. After briefly introducing the role of the transportome in cancer, we discuss TRP channel functions in cancer cell migration. We highlight the role of TRP channels in sensing and transmitting cues from the tumor microenvironment and discuss their role in cancer cell invasion. We identify open questions concerning the role of TRP channels in circulating tumor cells and in the processes of intra- and extravasation of tumor cells. We emphasize the importance of TRP channels in different steps of cancer metastasis and propose cancer-specific TRP channel blockade as a therapeutic option in cancer treatment.
细胞钙稳态失调与包括癌症在内的多种病理状况有关。通过离子通道和转运体（转运组）通量改变所引起的钙信号变化参与了转移级联反应的各个步骤。癌细胞借此“重新编程”并“滥用”细胞转运组来调节增殖、凋亡、代谢、生长因子信号传导、迁移和侵袭。在转移级联反应过程中，癌细胞利用其转运组来应对各种环境挑战，如缺氧、酸性和机械信号。因此，离子通道和转运体是癌症进展的关键调节因子。本综述重点关注瞬时受体电位（TRP）通道在转移级联反应中的作用。在简要介绍转运组在癌症中的作用后，我们讨论TRP通道在癌细胞迁移中的功能。我们强调TRP通道在感知和传递来自肿瘤微环境的信号中的作用，并讨论它们在癌细胞侵袭中的作用。我们确定了关于TRP通道在循环肿瘤细胞以及肿瘤细胞内渗和外渗过程中作用的未解决问题。我们强调TRP通道在癌症转移不同步骤中的重要性，并提出针对癌症的TRP通道阻断作为癌症治疗的一种治疗选择。
