Resistance of glioma cells to nutrient-deprived microenvironment can be enhanced by CD133-mediated autophagy.

// Haojie Sun 1, * , Mingzhi Zhang 1, * , Kai Cheng 2 , Peng Li 1 , Shuo Han 1 , Ruizhi Li 1 , Ming Su 1 , Wotan Zeng 3 , Jinwen Liu 3 , Jinhai Guo 3 , Yinan Liu 1 , Xiaoyan Zhang 1 , Qihua He 1 , Li Shen 1 1 Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People’s Republic of China 2 Department of Laboratory Medicine, Fenyang College of Shanxi Medical University, Fenyang, People’s Republic of China 3 Beijing DongFang YaMei Gene Science and Technology Research Institute, Beijing, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Li Shen, email: shenli@bjmu.edu.cn Qihua He, email: hqh@bjmu.edu.cn Keywords: CD133, autophagy, mTOR, Beclin1, Atg5 Received: February 28, 2016      Accepted: September 24, 2016      Published: October 21, 2016 ABSTRACT 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.