Autophagy impairment inhibits differentiation of glioma stem/progenitor cells.
Despite of similarities between glioma stem/progenitor cells (GSPCs) and neural stem/progenitor cells (NSPCs), inhibition of differentiation is a distinct characteristic of GSPCs. In this study, we investigated the effects of autophagy impairment on inhibition of differentiation of GSPC, and its molecular mechanism. GSPCs were kept by our laboratory; NSPCs were isolated from human fetal brain tissue. We found that the autophagic activity in GSPCs was significantly lower than that in NSPCs. However, the autophagic activity markedly increased after GSPCs were induced to differentiate by fetal calf serum (FCS). The autophagy inhibitors 3-methyladenine and Bafilomycin A1 (BFA) inhibited the FSC-induced differentiation of GSPCs. And autophagy activator Rapamycin could promote differentiation of GSPCs. In order to disclose whether the loss of PTEN in GSPC is related to the deficiency of autophagic activity in GSPCs (for PTEN being lost in the GSPCs studied by us), we introduced the wild type gene of PTEN into GSPCs, and found that the autophagic activity was restored significantly after the gene transduction. The low autophagic activity in GSPCs leads to the inhibition of differentiation of GSPCs, and the loss of PTEN in GSPCs probably is an underlying mechanism for the low autophagic activity in GSPCs. These results suggest that bust autophagic activity target at PTEN might be a potential therapy target for glioma therapy.
Zhao
Yaodong
Y
Department of Neurosurgery, 2nd Affiliated Hospital of Soochow University, Jiangsu, PR China.
Huang
Qiang
Q
Yang
Jicheng
J
Lou
Meiqing
M
Wang
Aidong
A
Dong
Jun
J
Qin
Zhenghong
Z
Zhang
Tianyi
T
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002103:Cadaverine / Q000031:analogs & derivatives; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology; D005910:Glioma / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D018942:Macrolides / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D014161:Transduction, Genetic
D002491:Central Nervous System Agents; D018942:Macrolides; C025946:3-methyladenine; C040929:bafilomycin A1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C008542:monodansylcadaverine; D000225:Adenine; D002103:Cadaverine; D020123:Sirolimus