title: Orai1 and STIM1 mediate SOCE and contribute to apoptotic resistance of pancreatic adenocarcinoma.
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.
authors.affiliation: 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.
authors.forename: Kateryna
authors.initials: K
authors.lastname: Kondratska
authors.affiliation: 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.
authors.forename: Artem
authors.initials: A
authors.lastname: Kondratskyi
authors.affiliation: 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.
authors.forename: Maya
authors.initials: M
authors.lastname: Yassine
authors.affiliation: 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.
authors.forename: Loic
authors.initials: L
authors.lastname: Lemonnier
authors.affiliation: 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.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Lepage
authors.affiliation: 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.
authors.forename: Angela
authors.initials: A
authors.lastname: Morabito
authors.affiliation: 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.
authors.forename: Roman
authors.initials: R
authors.lastname: Skryma
authors.affiliation: 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.
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000071740:ORAI1 Protein; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D034741:RNA, Small Interfering; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D003841:Deoxycytidine; D002118:Calcium; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: Apoptosis; Calcium; Chemotherapy; Pancreatic adenocarcinoma; Resistance; SOCE