Downregulation of type 3 inositol (1,4,5)-trisphosphate receptor decreases breast cancer cell migration through an oscillatory Ca(2+) signal.

Breast cancer remains a research priority due to its invasive phenotype. Although the role of ion channels in cancer is now well established, the role of inositol (1,4,5)-trisphosphate (IP(3)) receptors (IP(3)Rs) remains enigmatic. If the three IP(3)Rs subtypes expression have been identified in various cancers, little is known about their physiological role. Here, we investigated the involvement of IP(3)R type 3 (IP(3)R(3)) in the migration processes of three human breast cancer cell lines showing different migration velocities: the low-migrating MCF-7 and the highly migrating and invasive MDA-MB-231 and MDA-MB-435S cell lines. We show that a higher IP(3)R3 expression level, but not IP(3)R1 nor IP(3)R2, is correlated to a stronger cell line migration capacity and a sustained calcium signal. Interestingly, silencing of IP(3)R3 highlights an oscillating calcium signaling profile and leads to a significant decrease of cell migration capacities of the three breast cancer cell lines. Conversely, stable overexpression of IP(3)R3 in MCF-7 cells significantly increases their migration capacities. This effect is completely reversed by IP(3)R3 silencing. In conclusion, we demonstrate that IP(3)R3 expression level increases the migration capacity of human breast cancer cells by changing the calcium signature.