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Downregulation of type 3 inositol (1,4,5)-trisphosphate receptor decreases breast cancer cell migration through an oscillatory Ca2+ signal

2017; Impact Journals LLC; Volume: 8; Issue: 42 Linguagem: Inglês

10.18632/oncotarget.20327

1949-2553

Abdallah Mound, Alexia Vautrin-Glabik, Arthur Foulon, Béatrice Botia, Frédéric Hague, Jan B. Parys, Halima Ouadid‐Ahidouch, Lise Rodat‐Despoix,

Calcium signaling and nucleotide metabolism

// Abdallah Mound 1 , Alexia Vautrin-Glabik 1 , Arthur Foulon 1 , Béatrice Botia 1 , Frédéric Hague 1 , Jan B. Parys 2 , Halima Ouadid-Ahidouch 1 and Lise Rodat-Despoix 1 1 Laboratory 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 2 Laboratory of Molecular and Cellular Signalling, Department of Cellular and Molecular Medicine, Campus Gasthuisberg O/N1- bus 802-K U Leuven, B-3000 Leuven, Belgium Correspondence to: Lise Rodat-Despoix, email: lise.despoix@u-picardie.fr Keywords: breast cancer, migration, type 3 inositol 1,4,5-trisphosphate receptor, Ca 2+ Received: April 11, 2017 Accepted: August 04, 2017 Published: August 18, 2017 ABSTRACT 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.