{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sun C"],"funding":["NHLBI NIH HHS"],"pagination":["396"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6529459"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(6)"],"pubmed_abstract":["Ca2+ oscillation is a system-level property of the cellular Ca2+-handling machinery and encodes diverse physiological and pathological signals. The present study tests the hypothesis that Ca2+ oscillations play a vital role in maintaining the stemness of liver cancer stem cells (CSCs), which are postulated to be responsible for cancer initiation and progression. We found that niche factor-stimulated Ca2+ oscillation is a signature feature of CSC-enriched Hep-12 cells and purified α2δ1+ CSC fractions from hepatocellular carcinoma cell lines. In Hep-12 cells, the Ca2+ oscillation frequency positively correlated with the self-renewal potential. Using a newly developed high signal, endoplasmic reticulum (ER) localized Ca2+ sensor GCaMP-ER2, we demonstrated CSC-distinctive oscillatory ER Ca2+ release controlled by the type 2 inositol 1,4,5-trisphosphate receptor (IP3R2). Knockdown of IP3R2 severely suppressed the self-renewal capacity of liver CSCs. We propose that targeting the IP3R2-mediated Ca2+ oscillation in CSCs might afford a novel, physiologically inspired anti-tumor strategy for liver cancer."],"journal":["Cell death & disease"],"pubmed_title":["Central role of IP3R2-mediated Ca2+ oscillation in self-renewal of liver cancer stem cells elucidated by high-signal ER sensor."],"pmcid":["PMC6529459"],"funding_grant_id":["R24 HL120847"],"pubmed_authors":["Liu H","Lee JC","Doran R","Sun C","Zhao W","Sun T","Kotlikoff MI","Li W","Lee FK","Zhang Z","Shui B","Shen QS","Wang X","Reining S","Cheng H"],"additional_accession":[]},"is_claimable":false,"name":"Central role of IP3R2-mediated Ca2+ oscillation in self-renewal of liver cancer stem cells elucidated by high-signal ER sensor.","description":"Ca2+ oscillation is a system-level property of the cellular Ca2+-handling machinery and encodes diverse physiological and pathological signals. The present study tests the hypothesis that Ca2+ oscillations play a vital role in maintaining the stemness of liver cancer stem cells (CSCs), which are postulated to be responsible for cancer initiation and progression. We found that niche factor-stimulated Ca2+ oscillation is a signature feature of CSC-enriched Hep-12 cells and purified α2δ1+ CSC fractions from hepatocellular carcinoma cell lines. In Hep-12 cells, the Ca2+ oscillation frequency positively correlated with the self-renewal potential. Using a newly developed high signal, endoplasmic reticulum (ER) localized Ca2+ sensor GCaMP-ER2, we demonstrated CSC-distinctive oscillatory ER Ca2+ release controlled by the type 2 inositol 1,4,5-trisphosphate receptor (IP3R2). Knockdown of IP3R2 severely suppressed the self-renewal capacity of liver CSCs. We propose that targeting the IP3R2-mediated Ca2+ oscillation in CSCs might afford a novel, physiologically inspired anti-tumor strategy for liver cancer.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 May","modification":"2024-11-12T03:04:08.789Z","creation":"2019-06-06T23:18:17Z"},"accession":"S-EPMC6529459","cross_references":{"pubmed":["31113961"],"doi":["10.1038/s41419-019-1613-2"]}}