Na,K -ATP 酶对于维持几乎所有细胞的膜电位至关重要，其催化亚基有四种异构体 (α1-α4)。体积调节阴离子通道（VRAC）除了在细胞体积维持中发挥基本作用外，还在细胞死亡信号通路中发挥重要作用。首先，我们介绍肌动蛋白丝的破坏会导致 VRAC 功能障碍，从而引起癌细胞对顺铂的耐药性。接下来，我们总结了癌细胞膜微区中 Na ,K -ATPase α1-异构体 (α1NaK) 和 VRAC 之间的串扰介导的强心苷诱导的信号通路。在这种机制中，亚微摩尔浓度的强心苷与受体型 α1NaK 结合，产生 VRAC 活性，同时减缓癌细胞增殖。最后，我们总结了在癌细胞胞内囊泡中异常表达的α3NaK的病理生理功能。癌细胞即使在失去锚定的情况下也能存活，因为它们具有失巢凋亡的回避机制。在癌细胞脱离时，我们发现细胞内的 α3NaK 易位至质膜，这一事件有助于细胞的存活。有趣的是，强心苷抑制 α3NaK 易位和细胞存活。我们的研究结果可能为癌症药物的开发开辟新的机遇。

Na+,K+-ATPases are essential for maintaining the membrane potential in almost all cells, and their catalytic subunits have four isoforms (α1-α4). Volume-regulated anion channel (VRAC) plays an important role in the cell death signaling pathway in addition to its fundamental role in cell volume maintenance. First, we introduce that disruption of actin filaments cause the dysfunction of VRAC, which elicits resistance to cisplatin in the cancer cells. Next, we summarize the cardiac glycosides-induced signaling pathway mediated by the crosstalk between Na+,K+-ATPase α1-isoform (α1NaK) and VRAC in the membrane microdomain of the cancer cells. In this mechanism, sub-micromolar concentrations of cardiac glycosides bind to the receptor-type α1NaK, and generate VRAC activities concomitantly with a deceleration of cancer cell proliferation. Finally, we summarize the pathophysiological function of α3NaK, which is abnormally expressed in the intracellular vesicles of cancer cells. The cancer cell can survive even under loss of anchorage because they have the avoidance mechanism for anoikis. On cancer cell detachment, we found that intracellular α3NaK is translocated to the plasma membrane and this event contributes to the survival of the cells. Interestingly, cardiac glycosides inhibited the α3NaK translocation and cell survival. Our findings may open up new opportunities for the development of cancer medicines.