Reduction of breast cancer cell migration via up-regulation of TASK-3 two-pore domain K plus channel

Abstract

Aim: Many kinds of K+ channels are expressed in a variety of cells, including cancer cells. However, only a small amount of research has explored the relationship between voltage-independent K+ channels and breast cancer. This study was performed to investigate whether changes in two-pore domain K+ (K2P) channel expression levels are related to the migration of human breast cancer cells. Methods: K2P channel gene/ protein expression levels were compared between MCF-7 (a non-invasive cell) and MDA-MB-231 (an invasive cell) using reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blotting and immunocytochemistry. The relationship between K2P channel expression level and cell migration was analysed using gene overexpression and knock-down techniques. Functional expression of TASK3 in MCF-7 and MDA-MB-231 cells was recorded using patch-clamp technique. Results: Of K2P channels, TASK-3 mRNA and protein were highly expressed in MCF-7 cells compared with those in MDA-MB-231 cells. Overexpression of TASK-3 in breast cancer cells reduced migration and invasion, whereas silencing of TASK-3 increased the migration and invasion. The TASK-3 expression level was decreased by phorbol myristate acetate (PMA), a PKC activator. PMA also enhanced the cell migration in MDAMB- 231 cells. Conclusion: These results show that an increase in TASK-3 expression levels, which could be modulated by PKC activation, reduces cell migration/ invasion in breast cancer cells and suggest that modulation of TASK-3 expression may regulate metastasis of breast cancer cells.