Department of Surgery, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine and Cancer Center at the University of Hawaii, Honolulu, Hawaii 96813, USA.
Cell Calcium. 2022 Jan;101:102521. doi: 10.1016/j.ceca.2021.102521. Epub 2021 Dec 17.
TRPM7 is a non-selective divalent cation channel with an alpha-kinase domain. Corresponding with its broad expression, TRPM7 has a role in a wide range of cell functions, including proliferation, migration, and survival. Growing evidence shows that TRPM7 is also aberrantly expressed in various cancers, including brain cancers. Because ion channels have widespread tissue distribution and result in extensive physiological consequences when dysfunctional, these proteins can be compelling drug targets. In fact, ion channels comprise the third-largest drug target type, following enzymes and receptors. Literature has shown that suppression of TRPM7 results in inhibition of migration, invasion, and proliferation in several human brain tumours. Therefore, TRPM7 presents a potential target for therapeutic brain tumour interventions. This article reviews current literature on TRPM7 as a potential drug target in the context of brain tumours and provides an overview of various selective and non-selective modulators of the channel relevant to pharmacology, oncology, and ion channel function.
TRPM7 是一种非选择性二价阳离子通道，具有一个α-激酶结构域。与其广泛的表达相对应，TRPM7 在多种细胞功能中发挥作用，包括增殖、迁移和存活。越来越多的证据表明，TRPM7 在各种癌症中也异常表达，包括脑癌。由于离子通道在组织中有广泛的分布，如果功能失调会导致广泛的生理后果，因此这些蛋白质可以成为有吸引力的药物靶点。事实上，离子通道是继酶和受体之后第三大药物靶点类型。文献表明，抑制 TRPM7 可抑制几种人脑肿瘤的迁移、侵袭和增殖。因此，TRPM7 为治疗脑肿瘤的干预提供了一个潜在的靶点。本文综述了 TRPM7 作为脑肿瘤潜在药物靶点的相关文献，并概述了与药理学、肿瘤学和离子通道功能相关的通道的各种选择性和非选择性调节剂。
