Resistance of glioma cells to nutrient-deprived microenvironment can be enhanced by CD133-mediated autophagy.
Resistance of glioma cells to nutrient-deprived microenvironment can be enhanced by CD133-mediated autophagy.
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CD133介导的自噬可以增强胶质瘤细胞对营养匮乏的微环境的抵抗力。
DOI：
10.18632/oncotarget.12803
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发表时间：
2016-11-15
期刊：
影响因子：
--
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Sun H;Zhang M;Cheng K;Li P;Han S;Li R;Su M;Zeng W;Liu J;Guo J;Liu Y;Zhang X;He Q;Shen L
CD133是一种五聚体跨膜蛋白，可作为肿瘤干细胞的生物标志物，尽管其生化机制尚不清楚。在这里，我们报告CD133的表达增强了胶质瘤细胞对营养缺乏微环境的耐受性。在饥饿条件下，CD133阳性细胞表现出较高的存活率和较低的凋亡率。这些变化依赖于自噬相关基因信号的激活，并被自噬抑制剂氯喹所削弱。此外，雷帕霉素上调自噬水平，反之降低CD133的表达。免疫荧光证实，饥饿促进CD133从质膜释放到细胞质，饥饿时CD133也部分与LC3共定位。此外，CD133与Beclin1、ATG5和溶酶体部分共定位，表明CD133直接参与自噬体膜融合过程，最终经历溶酶体降解。总之，我们的结果表明，CD133通过调节自噬来促进细胞存活，靶向CD133连接的信号和自噬可能有助于改善抗癌治疗。
CD133 is a pentaspan transmembrane protein that can serve as a biomarker for cancer stem cells, although its biochemical mechanism remains unclear. Here we report that CD133 expression enhances glioma cell tolerance of a nutrient-deprived microenvironment. Under starvation conditions, CD133-positive cells exhibited higher survival and decreased levels of apoptosis. These changes were dependent on activation of autophagy-associated gene signaling and were impaired by the autophagic inhibitor chloroquine. Furthermore, rapamycin up-regulated the level of autophagy and inversely reduced CD133 expression. Immunofluorescence confirmed that starvation promoted release of CD133 from the plasma membrane to the cytoplasm, with CD133 also partially co-localizing with LC3 upon starvation. Additionally, CD133 partially co-localized with Beclin1, Atg5, and lysosomes, indicating that CD133 directly participates in the autophagosome membrane fusion process and ultimately undergoes lysosomal degradation. Collectively, our results demonstrate that CD133 contributes to cell survival by regulating autophagy, and that targeting CD133-linked signaling and autophagy may be useful in improving anti-cancer treatments.