Central role of IP3R2-mediated Ca2+ oscillation in self-renewal of liver cancer stem cells elucidated by high-signal ER sensor
| Autor: | Xianhua Wang, Frank K. Lee, Robert Doran, Tao Sun, Bo Shui, Heping Cheng, Michael I. Kotlikoff, Qing Sunny Shen, Jane C. Lee, Wenwen Li, Hui Liu, Shaun Reining, Wei Zhao, Cuiwei Sun, Zhiqian Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research lcsh:Cytology Chemistry Endoplasmic reticulum Immunology Cancer Cell Biology medicine.disease Cell biology Transplantation 03 medical and health sciences Cellular and Molecular Neuroscience 030104 developmental biology 0302 clinical medicine Cell culture 030220 oncology & carcinogenesis Cell Self Renewal medicine lcsh:QH573-671 Stem cell Liver cancer Receptor |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 6, Pp 1-13 (2019) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-019-1613-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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