National Center of Competence in Research NCCR TransCure, Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland.
Biomolecules. 2021 Feb 5;11(2):229. doi: 10.3390/biom11020229.
Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, liver, breast, urinary bladder, cervical, and endometrial cancer. In several types of cancer TRPM4 is overexpressed and contributes to cancer hallmark functions such as increased proliferation and migration and cell cycle shift. Hence, TRPM4 is a potential prognostic cancer marker and a promising anticancer drug target candidate. Currently, the underlying mechanism by which TRPM4 contributes to cancer hallmark functions is under investigation. TRPM4 is a Ca-activated monovalent cation channel, and its ion conductivity can decrease intracellular Ca signaling. Furthermore, TRPM4 can interact with different partner proteins. However, the lack of potent and specific TRPM4 inhibitors has delayed the investigations of TRPM4. In this review, we summarize the potential mechanisms of action and discuss new small molecule TRPM4 inhibitors, as well as the TRPM4 antibody, M4P. Additionally, we provide an overview of TRPM4 in human cancer and discuss TRPM4 as a diagnostic marker and anticancer drug target.
瞬时受体电位阳离子通道亚家族 M 成员 4（TRPM4）广泛表达于各种器官中，与心血管疾病和自身免疫性疾病相关。最近，人们对 TRPM4 在癌症中的研究产生了兴趣。迄今为止，TRPM4 已在弥漫性大 B 细胞淋巴瘤、前列腺癌、结直肠癌、肝癌、乳腺癌、膀胱癌、宫颈癌和子宫内膜癌中进行了研究。在几种类型的癌症中，TRPM4 过表达，并有助于癌症标志性功能，如增殖和迁移增加以及细胞周期转变。因此，TRPM4 是一种有潜力的预后癌症标志物和有前途的抗癌药物靶点候选物。目前，TRPM4 促进癌症标志性功能的潜在机制正在研究中。TRPM4 是一种 Ca2+激活的单价阳离子通道，其离子导电性可降低细胞内 Ca2+信号。此外，TRPM4 可以与不同的伴侣蛋白相互作用。然而，缺乏有效和特异的 TRPM4 抑制剂，阻碍了对 TRPM4 的研究。在这篇综述中，我们总结了潜在的作用机制，并讨论了新的小分子 TRPM4 抑制剂，以及 TRPM4 抗体 M4P。此外，我们概述了 TRPM4 在人类癌症中的作用，并讨论了 TRPM4 作为诊断标志物和抗癌药物靶点的潜力。
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