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10.1038/s41598-017-14230-1

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suck abstract from ncbi


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pmid29079724
      Sci+Rep 2017 ; 7 (1 ): 14199
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  • Ca(2+) protein alpha 1D of CaV1 3 regulates intracellular calcium concentration and migration of colon cancer cells through a non-canonical activity #MMPMID29079724
  • Fourbon Y ; Guéguinou M ; Félix R ; Constantin B ; Uguen A ; Fromont G ; Lajoie L ; Magaud C ; Lecomte T ; Chamorey E ; Chatelier A ; Mignen O ; Potier-Cartereau M ; Chantôme A ; Bois P ; Vandier C
  • Sci Rep 2017[Oct]; 7 (1 ): 14199 PMID29079724 show ga
  • It is generally accepted that voltage-gated Ca(2+) channels, CaV, regulate Ca(2+) homeostasis in excitable cells following plasma membrane depolarization. Here, we show that the Ca(2+) protein ?1D of CaV1.3 channel is overexpressed in colorectal cancer biopsies compared to normal tissues. Gene silencing experiments targeting ?1D reduced the migration and the basal cytosolic Ca(2+) concentration of HCT116 colon cancer cell line and modified the cytosolic Ca(2+) oscillations induced by the sodium/calcium exchanger NCX1/3 working in its reverse mode. Interestingly, NCX1/3 regulated membrane potential of HCT116 cells only when ?1D was silenced, and blocking NCX1/3 increased cytosolic Ca(2+) concentration and cell migration. However, membrane depolarization did not induce an increase in intracellular Ca(2+). Patch-clamp experiments clearly showed that the inward Ca(2+) current was absent. Finally, flow cytometry and immunofluorescence studies showed that ?1D protein was localized at the plasma membrane, in cytosol and cell nuclei. Altogether, we uncover a novel signaling pathway showing that ?1D is involved in the regulation of Ca(2+) homeostasis and cell migration by a mechanism independent of its plasma membrane canonical function but that involved plasma membrane Na(+)/Ca(2+) exchanger.
  • |*Cell Movement [MESH]
  • |Active Transport, Cell Nucleus [MESH]
  • |Calcium Channels, L-Type/*chemistry/*metabolism [MESH]
  • |Calcium/*metabolism [MESH]
  • |Cell Membrane/metabolism [MESH]
  • |Cell Nucleus/metabolism [MESH]
  • |Colonic Neoplasms/*metabolism/*pathology/physiopathology [MESH]
  • |Cytosol/metabolism [MESH]
  • |Electrophysiological Phenomena [MESH]
  • |Endoplasmic Reticulum/metabolism [MESH]
  • |Gene Expression Regulation, Neoplastic [MESH]
  • |HCT116 Cells [MESH]
  • |Humans [MESH]
  • |Intracellular Space/*metabolism [MESH]


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