Downregulation of type 3 inositol (1,4,5)-trisphosphate receptor decreases breast cancer cell migration through an oscillatory Ca2+ signal
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Abdallah Mound1, Alexia Vautrin-Glabik1, Arthur Foulon1, Béatrice Botia1, Frédéric Hague1, Jan B. Parys2, Halima Ouadid-Ahidouch1 and Lise Rodat-Despoix1
1Laboratory of Cellular and Molecular Physiology (EA-4667), “Ion Channels in Breast Cancer”, SFR CAP-SANTE (FED-4231), University of Amiens, UFR Sciences, 80039 Amiens, France
2Laboratory of Molecular and Cellular Signalling, Department of Cellular and Molecular Medicine, Campus Gasthuisberg O/N1- bus 802-K U Leuven, B-3000 Leuven, Belgium
Lise Rodat-Despoix, email: [email protected]
Keywords: breast cancer, migration, type 3 inositol 1,4,5-trisphosphate receptor, Ca2+
Received: April 11, 2017 Accepted: August 04, 2017 Published: August 18, 2017
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 (IP3) receptors (IP3Rs) remains enigmatic. If the three IP3Rs subtypes expression have been identified in various cancers, little is known about their physiological role. Here, we investigated the involvement of IP3R type 3 (IP3R3) 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 IP3R3 expression level, but not IP3R1 nor IP3R2, is correlated to a stronger cell line migration capacity and a sustained calcium signal. Interestingly, silencing of IP3R3 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 IP3R3 in MCF-7 cells significantly increases their migration capacities. This effect is completely reversed by IP3R3 silencing. In conclusion, we demonstrate that IP3R3 expression level increases the migration capacity of human breast cancer cells by changing the calcium signature.
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