Human ether-a-go-go-related gene K+ channels regulate shedding of leukemia cell-derived microvesicles.

Microvesicles (MVs) are released by various cancer cells, including leukemia cells. They can "hijack" membrane components from their parental cells and exert pleiotropic effects on tumor progression. Human ether-a-go-go-related gene (hERG1) K(+) channels are highly expressed in cancer cells and appear of exceptional importance in favoring cancer development. Given the attributes of MVs and hERG1 K(+) channels in disease progression, we investigated the putative relationship between hERG1 K(+) channels and MVs in leukemia. The protein content of MVs isolated from K562 cell supernatants was significantly higher than that from HL-60 cells. The molecular profile of these MVs showed that in addition to the myeloid lineage antigen (CD11b), MVs contained hERG1 K(+) channels. Interestingly, inhibition of hERG1 K(+) channels rapidly reduced MV fractions in supernatants. Furthermore, MVs created positive feedback loops to facilitate leukemogenesis. Upon exposure to MVs, the plasma membrane expression of hERG1 protein was in turn up-regulated, the migration of leukemia cells was significantly increased, and the adhesion of leukemia cells to human umbilical vein endothelial cells (HUVECs) was markedly enhanced. Importantly, hERG1 K(+) channel inhibitor E-4031 impaired these effects. We conclude that leukemia cell-derived MVs can "hijack" the plasma membrane hERG1 K(+) channels, which regulate the release of MVs and their biological effects upon leukemia cells.