ORAI3 silencing alters cell proliferation and promotes mitotic catastrophe and apoptosis in pancreatic adenocarcinoma
| Autor: | ZIENTAL GELUS , Nathalie, Vanden Abeele, Fabien, DUBOIS, Charlotte, Kondratska, Kateryna, Kondratskyi, Artem, MORABITO, Angela, MESILMANY, Lina, Farfariello, Valerio, Toillon, Robert-Alain, Gelus, Nathalie, LAURENGE, Emilie, Lemonnier, Loic, Prevarskaya, Natalia |
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| Přispěvatelé: | Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Signalisation des facteurs de croissance dans le cancer du sein. Protéomique fonctionnelle, Institut National de la Santé et de la Recherche Médicale (INSERM), DUBOIS, Charlotte |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death ORAI1 Protein Mitosis Apoptosis [SDV.BC]Life Sciences [q-bio]/Cellular Biology Adenocarcinoma 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Gene silencing Humans Calcium Signaling Gene Silencing RNA Small Interfering [SDV.BC] Life Sciences [q-bio]/Cellular Biology Molecular Biology Mitotic catastrophe Cell Proliferation Cell growth Chemistry ORAI1 PDAC Cell Biology Cell cycle Store-operated calcium entry Cell biology Gene Expression Regulation Neoplastic Pancreatic Neoplasms ORAI3 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Calcium Calcium Channels |
| Zdroj: | Biochimica et Biophysica Acta-Molecular Cell Research Biochimica et Biophysica Acta-Molecular Cell Research, Elsevier, 2021, 1868 (7), pp.119023. ⟨10.1016/j.bbamcr.2021.119023⟩ Biochimica et Biophysica Acta-Molecular Cell Research, 2021, 1868 (7), pp.119023. ⟨10.1016/j.bbamcr.2021.119023⟩ |
| ISSN: | 1879-2596 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2021.119023⟩ |
| Popis: | International audience; Changes in cytosolic free Ca2+ concentration play a central role in many fundamental cellular processes including muscle contraction, neurotransmission, cell proliferation, differentiation, gene transcription and cell death. Many of these processes are known to be regulated by store-operated calcium channels (SOCs), among which ORAI1 is the most studied in cancer cells, leaving the role of other ORAI channels yet inadequately addressed. Here we demonstrate that ORAI3 channels are expressed in both normal (HPDE) and pancreatic ductal adenocarcinoma (PDAC) cell lines, where they form functional channels, their knockdown affecting store operated calcium entry (SOCE). More specifically, ORAI3 silencing increased SOCE in PDAC cell lines, while decreasing SOCE in normal pancreatic cell line. We also show the role of ORAI3 in proliferation, cell cycle, viability, mitotic catastrophe and cell death. Finally, we demonstrate that ORAI3 silencing impairs pancreatic tumor growth and induces cell death in vivo, suggesting that ORAI3 could represent a potential therapeutic target in PDAC treatment. |
| Databáze: | OpenAIRE |
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