Department of Surgery, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada.
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada.
Cell Calcium. 2021 Jun;96:102400. doi: 10.1016/j.ceca.2021.102400. Epub 2021 Mar 22.
Cancer is the second leading cause of death worldwide and accounted for an estimated 9.6 million deaths, or 1 in 6 deaths, in 2018. Despite recent advances in cancer prevention, diagnosis, and treatment strategies, the burden of this disease continues to grow with each year, with dire physical, emotional, and economic consequences for all levels of society. Classic characteristics of cancer include rapid, uncontrolled cell proliferation and spread of cancerous cells to other parts of the body, a process known as metastasis. Transient receptor potential melastatin 7 (TRPM7), a Ca- and Mg-permeable nonselective divalent cation channel defined by the atypical presence of an α-kinase within its C-terminal domain, has been implicated, due to its modulation of Ca and Mg influx, in a wide variety of physiological and pathological processes, including cancer. TRPM7 is overexpressed in several cancer types and has been shown to variably increase cellular proliferation, migration, and invasion of tumour cells. However, the relative contribution of TRPM7 kinase domain activity to cancer as opposed to ion flux through its channel pore remains an area of active discovery. In this review, we describe the specific role of the TRPM7 kinase domain in cancer processes as well as mechanisms of regulation and inhibition of the kinase domain.
癌症是全球第二大死亡原因，据估计，2018 年有 960 万人因此死亡，占总死亡人数的 1/6。尽管近年来在癌症预防、诊断和治疗策略方面取得了进展，但这种疾病的负担仍在逐年增加，给社会各阶层带来了严重的身体、情感和经济后果。癌症的典型特征包括快速、不受控制的细胞增殖和癌细胞向身体其他部位的扩散，这一过程称为转移。瞬时受体电位 melastatin 7（TRPM7）是一种 Ca2+和 Mg2+可通透的非选择性二价阳离子通道，其 C 端结构域内存在非典型的α-激酶，由于其对 Ca2+和 Mg2+内流的调节，参与了广泛的生理和病理过程，包括癌症。TRPM7 在多种癌症类型中过表达，并已被证明可不同程度地增加肿瘤细胞的增殖、迁移和侵袭。然而，TRPM7 激酶结构域活性对癌症的相对贡献与通过其通道孔的离子流相比，仍然是一个活跃的研究领域。在这篇综述中，我们描述了 TRPM7 激酶结构域在癌症过程中的特定作用，以及激酶结构域的调节和抑制机制。
