Kondratska Kateryna, Kondratskyi Artem, Yassine Maya, Lemonnier Loic, Lepage Gilbert, Morabito Angela, Skryma Roman, Prevarskaya Natalia
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.
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.
Biochim Biophys Acta. 2014 Oct;1843(10):2263-9. doi: 10.1016/j.bbamcr.2014.02.012. Epub 2014 Feb 26.
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.
store-operated钙通道（SOCs）是非兴奋性细胞中主要的钙内流途径之一。SOCs，尤其是其主要成分ORAI1和STIM1，已被证明与许多生理和病理过程有关，如细胞凋亡、增殖和侵袭。在这里，我们证明ORAI1和STIM1介导胰腺腺癌细胞系中的钙库操纵性钙内流（SOCE）。我们发现，ORAI1和STIM1在胰腺腺癌细胞系中都发挥着促生存的抗凋亡作用，因为小干扰RNA介导的ORAI1和/或STIM1敲低会增加化疗药物5-氟尿嘧啶（5-FU）或吉西他滨诱导的细胞凋亡。我们还证明，5-FU和吉西他滨处理均通过上调ORAI1和STIM1来增加Panc1胰腺腺癌细胞系中的SOCE。总之，我们的结果揭示了化疗药物5-FU和吉西他滨新的钙依赖性作用机制，并强调了ORAI1和STIM1在胰腺腺癌细胞中的抗凋亡作用。本文是名为“健康与疾病中的钙信号传导”特刊的一部分。客座编辑：Geert Bultynck、Jacques Haiech、Claus W. Heizmann、Joachim Krebs和Marc Moreau。
