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ORAI3 silencing alters cell proliferation and promotes mitotic catastrophe and apoptosis in pancreatic adenocarcinoma.

Abstract : 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.
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https://www.hal.inserm.fr/inserm-03237118
Contributor : Charlotte DUBOIS Connect in order to contact the contributor
Submitted on : Wednesday, May 26, 2021 - 3:18:55 PM
Last modification on : Wednesday, March 23, 2022 - 3:51:18 PM
Long-term archiving on: : Friday, August 27, 2021 - 8:05:24 PM

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Nathalie Ziental Gelus, Fabien Vanden Abeele, Charlotte Dubois, Kateryna Kondratska, Artem Kondratskyi, et al.. ORAI3 silencing alters cell proliferation and promotes mitotic catastrophe and apoptosis in pancreatic adenocarcinoma.. Biochimica et Biophysica Acta - Molecular Cell Research, Elsevier, 2021, 1868 (7), pp.119023. ⟨10.1016/j.bbamcr.2021.119023⟩. ⟨inserm-03237118⟩

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