Voltage-Gated K+ Channels Promote BT-474 Breast Cancer Cell Migration

Abstract

Objective: A variety of ion channels have been implicated in breast cancer proliferation and metastasis. Voltage-gated K+ (Kv) channels not only cause repolarization in excitable cells, but are also involved in multiple cellular functions in nonexcitable cells. In this study we investigated the role of Kv channels in migration of BT474 breast cancer cells. Methods: Transwell technique was used to separate migratory cells from nonmigratory ones and these 2 groups of cells were subject to electrophysiological examinations and microfluorimetric measurements for cytosolic Ca2+. Cell migration was examined in the absence or presence of Kv channel blockers. Results: When compared with nonmigratory cells, migratory cells had much higher Kv current densities, but rather unexpectedly, more depolarized membrane potential and reduced Ca2+ influx. PCR analysis revealed the presence of Kv1.4, Kv1.5, Kv1.6, Kv2.1 and Kv3.1 channels. Cell migration was markedly inhibited by tetraethylammonium, a delayed rectifier Kv channel blocker, but not by 4-aminopyridine, an A-type Kv blocker. Conclusion: Taken together, our results show that increased Kv channel expression played a role in BT474 cell migration, and Kv channels could be considered as biomarkers or potential therapeutic targets for breast cancer metastasis. The mechanism(s) by which Kv channels enhanced migration appeared unrelated to membrane hyperpolarization and Ca2+ influx.