The Kv10.1 potassium channel, driver of hypoxia-induced EMT and breast cancer cell aggressiveness.

BACKGROUND: Kv10.1 potassium channel has been shown to be involved in breast cancer luminal cell proliferation and survival as well as migration in basal cell model in normoxia. Moreover, it is clearly established that solid tumors present a hypoxic center. Currently, few information is available about the involvement of the Kv10.1 channel in hypoxic context in breast cancer progression. METHODS: We explored the role of Kv10.1 in the hypoxia-induced aggressiveness promotion of different breast cancer cell models: luminal A (MCF-7 cells), HER2-overexpressing (SKBr3 cells) and basal subtype (MDA-MB-231 cells) by using complementary approaches of cell biology assay, western blot and qPCR. RESULTS: Our results show that Kv10.1 expression and function are related to hypoxia and HIF-1α. Under hypoxia, we demonstrated that Kv10.1 is a major actor of the migration and it regulates the hypoxia-induced EMT in the three cells models by promoting the mesenchymal phenotype. Finally, after RNAseq comparison of cells expressing or not the channel in hypoxia condition, we highlighted the involvement of the β1-integrin / FAK, AKT and ERK pathways in the MDA-MB-231 breast cancer cell aggressiveness. CONCLUSION: We demonstrated, for the first time, the impact of Kv10.1 channel in hypoxia-induced aggressivity of breast cancer cells demonstrating its potential use as a complementary target to fight against metastasis development.