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Acidosis enhances the self-renewal and mitochondrial respiration of stem cell-like glioma cells through CYP24A1-mediated reduction of vitamin D

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机构: [1]State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 100005 Beijing, China. [2]Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. [3]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. [4]Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming, China
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Acidosis is a significant feature of the tumor microenvironment in glioma, and it is closely related to multiple biological functions of cancer stem cells. Here, we found that the self-renewal ability, the mitochondrial activity and ATP production were elevated in stem cell-like glioma cells (SLCs) under acidic microenvironment, which promoted and maintained the stemness of SLCs. Under acidosis, 25-hydroxy vitamin D-3-24-hydroxylase (CYP24A1) was upregulated and catalyzed the fast degradation of 1 alpha,25(OH)(2)D-3. We further revealed that the active form of vitamin D (1 alpha,25(OH)(2)D-3) could inhibit the expression of stemness markers, attenuate acidosis-induced increase of self-renewal ability and mitochondrial respiration in stem cell-like glioma cells. Our study indicates that the acidosis-CYP24A1-vitamin D pathway may be a key regulator of the cancer stem cell phenotype in malignant glioma and point out the potential value for the utilization of vitamin D to target cancer stem cells and to restrain the growth of malignant glioma in the future.

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出版当年[2018]版:
大类 | 2 区 生物
小类 | 2 区 细胞生物学
最新[2023]版:
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
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出版当年[2017]版:
Q1 CELL BIOLOGY
最新[2023]版:
Q1 CELL BIOLOGY

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第一作者机构: [1]State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 100005 Beijing, China.
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通讯机构: [1]State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 100005 Beijing, China. [4]Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming, China
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