BKCa promotes growth and metastasis of prostate cancer through facilitating the coupling between αvβ3 integrin and FAK

Abstract

BKCa is a large conductance calcium activated potassium channel promoting prostate cancer cell proliferation, although the mechanism is not fully elucidated. In addition, whether BKCa is involved in metastasis of prostate cancer remains to be explored. Here, we report that BKCa is overexpressed in prostate cancer. BKCa expression positively correlates with Ki67 index and gleason score of prostate cancer. Upregulation of BKCa promoted proliferation, migration and invasion of prostate cancer cells. On the contrary, downregulation of BKCa inhibited growth and metastasis of prostate cancer cells both in vitro and in vivo. Moreover, the ion-conducting function of BKCa contributed moderately to prostate cancer proliferation and migration, although, this was not the primary mechanism. BKCa action was mainly mediated through forming a functional complex with αvβ3 integrin. The BKCa/αvβ3 integrin complex promoted FAK phosphorylation independent of the channel activity. Overexpression of BKCa enhanced its association with αvβ3 integrin and FAK which increased FAK phosphorylation. Conversely, disrupting the complex by downregulation of BKCa reduced FAK phosphorylation. Finally, blocking of αvβ3 integrin or p-FAK activity using LM609 or Y15 markedly abrogated BKCa-enhanced cell proliferation and migration. Taken together, these results suggest that targeting BKCa/αvβ3/FAK may inaugurate innovative approaches to inhibit prostate cancer growth and metastasis.