Acidosis enhances the self-renewal and mitochondrial respiration of stem cell-like glioma cells through CYP24A1-mediated reduction of vitamin D.
Hu P1, Li S1, Tian N1, Wu F2, Hu Y1, Li D1, Qi Y1, Wei Z1, Wei Q1, Li Y1, Yin B1, Jiang T2,3, Yuan J1, Qiang B1, Han W4, Peng X5,6.
Cell Death Dis. 2019 Jan 10;10(1):25.
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 D3-24-hydroxylase (CYP24A1) was upregulated and catalyzed the fast degradation of 1α,25(OH)2D3. We further revealed that the active form of vitamin D (1α,25(OH)2D3) 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.