Resistance of glioma cells to nutrient-deprived microenvironment can be enhanced by CD133-mediated autophagy
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Haojie Sun1,*, Mingzhi Zhang1,*, Kai Cheng2, Peng Li1, Shuo Han1, Ruizhi Li1, Ming Su1, Wotan Zeng3, Jinwen Liu3, Jinhai Guo3, Yinan Liu1, Xiaoyan Zhang1, Qihua He1, Li Shen1
1Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People’s Republic of China
2Department of Laboratory Medicine, Fenyang College of Shanxi Medical University, Fenyang, People’s Republic of China
3Beijing DongFang YaMei Gene Science and Technology Research Institute, Beijing, People’s Republic of China
*These authors have contributed equally to this work
Li Shen, email: firstname.lastname@example.org
Qihua He, email: email@example.com
Keywords: CD133, autophagy, mTOR, Beclin1, Atg5
Received: February 28, 2016 Accepted: September 24, 2016 Published: October 21, 2016
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.
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