| Author |
Yassine, Maya Morabito, Angela Skryma, Roman Lepage, Gilbert Kondratska, Kateryna Kondratskyi, Artem Lemonnier, Loic Prevarskaya, Natalia |
| Description |
Author Affiliation: Kondratska K ( Inserm U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence, Ion Channels Science and Therapeutics, Université Lille 1, Villeneuve d'Ascq, France.); Kondratskyi A ( Inserm U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence, Ion Channels Science and Therapeutics, Université Lille 1, Villeneuve d'Ascq, France.); Yassine M ( Inserm U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence, Ion Channels Science and Therapeutics, Université Lille 1, Villeneuve d'Ascq, France.); Lemonnier L ( Inserm U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence, Ion Channels Science and Therapeutics, Université Lille 1, Villeneuve d'Ascq, France.); Lepage G ( Inserm U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence, Ion Channels Science and Therapeutics, Université Lille 1, Villeneuve d'Ascq, France.); Morabito A ( Inserm U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence, Ion Channels Science and Therapeutics, Université Lille 1, Villeneuve d'Ascq, France.); Skryma R ( Inserm U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence, Ion Channels Science and Therapeutics, Université Lille 1, Villeneuve d'Ascq, France.); Prevarskaya N ( Inserm U-1003, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Laboratory of Excellence, Ion Channels Science and Therapeutics, Université Lille 1, Villeneuve d'Ascq, France. Electronic address: Natacha.Prevarskaya@univ-lille1.fr.) |
| Abstract |
The store-operated calcium channels (SOCs) represent one of the major calcium-entry pathways in non-excitable cells. SOCs and in particular their major components ORAI1 and STIM1 have been shown to be implicated in a number of physiological and pathological processes such as apoptosis, proliferation and invasion. Here we demonstrate that ORAI1 and STIM1 mediate store-operated calcium entry (SOCE) in pancreatic adenocarcinoma cell lines. We show that both ORAI1 and STIM1 play pro-survival anti-apoptotic role in pancreatic adenocarcinoma cell lines, as siRNA-mediated knockdown of ORAI1 and/or STIM1 increases apoptosis induced by chemotherapy drugs 5-fluorouracil (5-FU) or gemcitabine. We also demonstrate that both 5-FU and gemcitabine treatments increase SOCE in Panc1 pancreatic adenocarcinoma cell line via upregulation of ORAI1 and STIM1. Altogether our results reveal the novel calcium-dependent mechanism of action of the chemotherapy drugs 5-FU and gemcitabine and emphasize the anti-apoptotic role of ORAI1 and STIM1 in pancreatic adenocarcinoma cells. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau. |
