期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1868, 期 7, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2021.119023
关键词
Calcium channels; ORAI3; Mitotic catastrophe; Apoptosis; PDAC
资金
- INSERM
- Ligue Nationale Contre le Cancer
- Ministere de l'Education Nationale
- La fondation de France
- I-SITE ULNE
- Hauts de France
Changes in cytosolic free Ca2+ concentration play a central role in cellular processes. ORAI3 channels are expressed in both normal and pancreatic ductal adenocarcinoma cell lines, affecting store-operated calcium entry (SOCE). Silencing ORAI3 increases SOCE in PDAC cell lines and decreases SOCE in normal pancreatic cell line, impacting proliferation, cell cycle, viability, mitotic catastrophe, and cell death.
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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