ER stress inducer tunicamycin suppresses the self-renewal of glioma-initiating cell partly through inhibiting Sox2 translation.
Glioma-initiating cells possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Therefore, their elimination is an essential factor for the development of efficient therapy. Here, we report that endoplasmic reticulum (ER) stress inducer tunicamycin inhibits glioma-initiating cell self-renewal as determined by neurosphere formation assay. Moreover, tunicamycin decreases the efficiency of glioma-initiating cell to initiate tumor formation. Although tunicamycin induces glioma-initiating cell apoptosis, apoptosis inhibitor z-VAD-fmk only partly abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Indeed, tunicamycin reduces the expression of self-renewal regulator Sox2 at translation level. Overexpression of Sox2 obviously abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Taken together, tunicamycin suppresses the self-renewal and tumorigenic potential of glioma-initiating cell partly through reducing Sox2 translation. This finding provides a cue to potential effective treatment of glioblastoma through controlling stem cells.
Key Laboratory of Glycoconjuates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.
Yang
Y
Xing
Key Laboratory of Glycoconjuates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.
Yuqing
Y
Ge
Key Laboratory of Glycoconjuates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.
Chanjuan
C
Liu
Division of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Xiaobiao
X
Zhang
Key Laboratory of Glycoconjuates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.
Jianhai
J
Jiang
Key Laboratory of Glycoconjuates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, People's Republic of China.
Yuanyan
Y
Wei
D000818:Animals; D015153:Blotting, Western; D000066673:Cell Self Renewal / Q000187:drug effects* / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D055748:SOXB1 Transcription Factors; D014415:Tunicamycin
Sox2; glioma-initiating cell; self-renewal; tunicamycin