Calcium Signalling Laboratory, National Neuroscience Institute, Singapore.
Calcium Signalling Laboratory, National Neuroscience Institute, Singapore; Duke-NUS Medical School, Singapore; Health and Social Sciences, Singapore Institute of Technology, Singapore.
Cancer Lett. 2019 Jul 10;454:66-69. doi: 10.1016/j.canlet.2019.04.012. Epub 2019 Apr 10.
The TRPM4 channel has been extensively studied in cerebral diseases such as stroke, head injury and multiple sclerosis. In the heart, gain-of-function mutations of TRPM4 are a cause of familial cardiac block. Recently, evidence has emerged to support the role of TRPM4 in certain types of cancer, such as prostate cancer and large B cell lymphoma. The expression of TRPM4 could mediate certain behaviors of cancer cells such as migration and invasion. However, the mechanisms are largely unknown. As a nonselective monovalent cation channel, TRPM4 upregulation and activation enhance sodium entry, which leads to depolarization of the membrane potential. The membrane potential is critical in regulating calcium influx, and a disturbed calcium homeostasis is always associated with cancer cell behaviors. Research on TRPM4 channels in cancer is at a very early stage. In this review, we summarize the expression of TRPM4 in various cancers as well as our current understanding of TRPM4 in cancer. The potential mechanisms of the TRPM4 channel in regulating calcium homeostasis in cancer cells are further discussed in detail. Targeting the TRPM4 channel can be a novel way of managing cancer metastasis via disrupting calcium signaling pathways.
TRPM4 通道在脑疾病（如中风、头部损伤和多发性硬化症）中已被广泛研究。在心脏中，TRPM4 的功能获得性突变是家族性心脏阻滞的一个原因。最近，有证据表明 TRPM4 在某些类型的癌症中起作用，如前列腺癌和大 B 细胞淋巴瘤。TRPM4 的表达可以介导癌细胞的某些行为，如迁移和侵袭。然而，其机制在很大程度上尚不清楚。作为一种非选择性单价阳离子通道，TRPM4 的上调和激活增强了钠离子的进入，导致膜电位去极化。膜电位在调节钙离子内流中至关重要，而钙稳态的紊乱总是与癌细胞的行为有关。目前，对癌症中 TRPM4 通道的研究还处于起步阶段。在这篇综述中，我们总结了 TRPM4 在各种癌症中的表达以及我们目前对 TRPM4 在癌症中的理解。进一步详细讨论了 TRPM4 通道在调节癌细胞钙稳态中的潜在机制。靶向 TRPM4 通道可能是通过破坏钙信号通路来控制癌症转移的一种新方法。
