An inhibitor of K+ channels modulates human endometrial tumor-initiating cells

A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA), was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was also found to inhibit growth in vitro.These studies suggest that the activity of potassium channels significantly contributes to the progression of endometrial tumors, and the antagonists of potassium channels are candidate anti-cancer drugs to specifically target tumor initiating cells in endometrial cancer therapy.Potassium (K+) ion channels are important contributors to the malignant phenotype in cancer cells and as such have been shown to drive progression of cancers of the breast, prostate, endometrium and brain [1-8]. Multiple mechanisms exist by which K+ channels exert their oncogenic functions. For example, K+ channels have been shown to modulate cell cycle progression to increase cell proliferation as well as promote cytoskeletal remodeling to enhance invasion and migration [9-21]. Inhibitors of K+ channels thus constitute putative anti-cancer drugs [1,2,22-26], though to date none of these antagonists have been explored in a clinical trial setting for any type of cancer.Novel developments in cancer research demonstrate that tumor initiating cells (TIC, also referred to as cancer stem cells) cause the onset and recurrence of cancers [27-29]. Several biological agents that aim to eradicate TIC are currently in phase I/II clinical trials, but a clinical need remains to identify other pharmacologic approaches to prevent TIC-mediated tumorigenesis.Interestingly, K+ channels genes have been shown to be amplified in cancers, but the roles of K+ channels in TIC and by extension in cancer progression have not been rigorously addressed. In this manuscript, we present novel observations that an