Wong Kah Keng, Banham Alison H, Yaacob Nik Soriani, Nur Husna Siti Muhamad
Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
J Cell Physiol. 2019 Sep;234(9):14556-14573. doi: 10.1002/jcp.28168. Epub 2019 Feb 2.
Transient receptor potential (TRP) proteins are a diverse family of ion channels present in multiple types of tissues. They function as gatekeepers for responses to sensory stimuli including temperature, vision, taste, and pain through their activities in conducting ion fluxes. The TRPM (melastatin) subfamily consists of eight members (i.e., TRPM1-8), which collectively regulate fluxes of various types of cations such as K , Na , Ca , and Mg . Growing evidence in the past two decades indicates that TRPM ion channels, their isoforms, or long noncoding RNAs encoded within the locus may be oncogenes involved in the regulation of cancer cell growth, proliferation, autophagy, invasion, and epithelial-mesenchymal transition, and their significant association with poor clinical outcomes of cancer patients. In this review, we describe and discuss recent findings implicating TRPM channels in different malignancies, their functions, mechanisms, and signaling pathways involved in cancers, as well as summarizing their normal physiological functions and the availability of ion channel pharmacological inhibitors.
瞬时受体电位(TRP)蛋白是存在于多种组织中的一类多样的离子通道家族。它们通过介导离子通量的活动,作为对包括温度、视觉、味觉和疼痛在内的感觉刺激做出反应的守门人。TRPM(褪黑素)亚家族由八个成员组成(即TRPM1 - 8),它们共同调节各种类型阳离子(如钾离子、钠离子、钙离子和镁离子)的通量。过去二十年中越来越多的证据表明,TRPM离子通道、其亚型或该基因座内编码的长链非编码RNA可能是参与调节癌细胞生长、增殖、自噬、侵袭和上皮 - 间质转化的癌基因,并且它们与癌症患者不良临床结局存在显著关联。在本综述中,我们描述并讨论了涉及TRPM通道在不同恶性肿瘤中的最新发现、它们在癌症中的功能、机制和信号通路,以及总结它们的正常生理功能和离子通道药理学抑制剂的可用性。