title: Resistance of glioma cells to nutrient-deprived microenvironment can be enhanced by CD133-mediated autophagy.
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.
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Haojie
authors: H
authors: Sun
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Mingzhi
authors: M
authors: Zhang
authors: Department of Laboratory Medicine, Fenyang College of Shanxi Medical University, Fenyang, People's Republic of China.
authors: Kai
authors: K
authors: Cheng
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Peng
authors: P
authors: Li
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Shuo
authors: S
authors: Han
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Ruizhi
authors: R
authors: Li
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Ming
authors: M
authors: Su
authors: Beijing DongFang YaMei Gene Science and Technology Research Institute, Beijing, People's Republic of China.
authors: Wotan
authors: W
authors: Zeng
authors: Beijing DongFang YaMei Gene Science and Technology Research Institute, Beijing, People's Republic of China.
authors: Jinwen
authors: J
authors: Liu
authors: Beijing DongFang YaMei Gene Science and Technology Research Institute, Beijing, People's Republic of China.
authors: Jinhai
authors: J
authors: Guo
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Yinan
authors: Y
authors: Liu
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Xiaoyan
authors: X
authors: Zhang
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Qihua
authors: Q
authors: He
authors: Department of Cell Biology, Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors: Li
authors: L
authors: Shen
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics / Q000378:metabolism*; D000071182:Autophagosomes / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D045744:Cell Line, Tumor; D004734:Energy Metabolism; D015870:Gene Expression; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D021381:Protein Transport; D015398:Signal Transduction; D013217:Starvation / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D000071916:AC133 Antigen; D008869:Microtubule-Associated Proteins
keywords: Atg5; Beclin1; CD133; autophagy; mTOR