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.研究所北京市神经外科研究所首都医科大学附属天坛医院[3]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[4]Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming, China
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.
基金:
National Key Research and Development Program of China [2016YFC0902500, 2016YFC0902502, 2016YFA0100702]; National Sciences Foundation of ChinaNational Natural Science Foundation of China [21874156, 31671316, 31670789]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-001, 2016-I2M-2-001, 2016-I2M-1-004, 2017-I2M-2-004, 2017-I2M-3-010, 2017-I2M-1-004]
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.
通讯作者:
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
推荐引用方式(GB/T 7714):
Hu Peishan,Li Shanshan,Tian Ningyu,et al.Acidosis enhances the self-renewal and mitochondrial respiration of stem cell-like glioma cells through CYP24A1-mediated reduction of vitamin D[J].CELL DEATH & DISEASE.2019,10(1):-.doi:10.1038/s41419-018-1242-1.
APA:
Hu, Peishan,Li, Shanshan,Tian, Ningyu,Wu, Fan,Hu, Yan...&Peng, Xiaozhong.(2019).Acidosis enhances the self-renewal and mitochondrial respiration of stem cell-like glioma cells through CYP24A1-mediated reduction of vitamin D.CELL DEATH & DISEASE,10,(1)
MLA:
Hu, Peishan,et al."Acidosis enhances the self-renewal and mitochondrial respiration of stem cell-like glioma cells through CYP24A1-mediated reduction of vitamin D".CELL DEATH & DISEASE 10..1(2019):-