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

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 TASK‐3 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 MDA‐MB‐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.