体内每个细胞的正常功能取决于其生物电特性，许多疾病是由潜在离子通道的遗传和/或表观遗传失调引起的。转移是癌症死亡的主要原因，是一个复杂的多阶段过程，其中细胞脱离原发肿瘤，侵入周围组织，通过遇到血管进入循环并扩散到全身，最终驻留在远处器官并增殖形成继发性肿瘤，导致毁灭性的器官衰竭。众所周知，这种细胞行为涉及离子通道。 CELEX 模型为转移提供了一种新颖的见解，其中癌细胞的电激发导致了它们的攻击性和侵袭性行为。反过来，过度兴奋性是由功能性电压门控钠通道的同时上调和电压门控钾通道的下调所支撑的。在这里，我们更新了支持 CELEX 癌症模型的体外和体内证据。对于钠通道来说，结果是明确的。钾通道臂也得到现有证据的广泛支持，尽管这些数据因通道对膜电位的影响和随之而来的次级效应而变得复杂。最后，与 CELEX 模型一致，我们表明（i）癌症确实是可电兴奋的并且能够产生动作电位，并且（ii）钠通道抑制剂和钾通道开放剂的组合可以产生强效的附加抗侵袭性影响。我们讨论了 CELEX 模型在癌症治疗中可能的临床意义。© 2024。作者。

The normal functioning of every cell in the body depends on its bioelectric properties and many diseases are caused by genetic and/or epigenetic dysregulation of the underlying ion channels. Metastasis, the main cause of death from cancer, is a complex multi-stage process in which cells break away from a primary tumour, invade the surrounding tissues, enter the circulation by encountering a blood vessel and spread around the body, ultimately lodging in distant organs and reproliferating to form secondary tumours leading to devastating organ failure. Such cellular behaviours are well known to involve ion channels. The CELEX model offers a novel insight to metastasis where it is the electrical excitation of the cancer cells that is responsible for their aggressive and invasive behaviour. In turn, the hyperexcitability is underpinned by concomitant upregulation of functional voltage-gated sodium channels and downregulation of voltage-gated potassium channels. Here, we update the in vitro and in vivo evidence in favour of the CELEX model for carcinomas. The results are unequivocal for the sodium channel. The potassium channel arm is also broadly supported by existing evidence although these data are complicated by the impact of the channels on the membrane potential and consequent secondary effects. Finally, consistent with the CELEX model, we show (i) that carcinomas are indeed electrically excitable and capable of generating action potentials and (ii) that combination of a sodium channel inhibitor and a potassium channel opener can produce a strong, additive anti-invasive effect. We discuss the possible clinical implications of the CELEX model in managing cancer.© 2024. The Author(s).