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PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype

Submit Time: 2016-05-15
Author: Duan, Shunlei 1 ; Yuan, Guohong 1 ; Ren, Ruotong 1 ; Xu, Xiuling 1 ; Fu, Lina 1 ; Li, Ying 1 ; Yang, Jiping 1 ; Zhang, Weiqi 1 ; Liu, Guang-Hui 1 ; Liu, Xiaomeng 2 ; Li, Jingyi 2 ; Tang, Fuchou 2 ; Ren, Ruotong 3 ; Bai, Ruijun 3 ; Liu, Guang-Hui 3 ; Ren, Ruotong 4 ; Bai, Ruijun 4 ; Qu, Jing 4 ; Zhang, Weizhou 5 ; Wu, Jun 6 ; Suzuki, Keiichiro 6 ; Esteban, Concepcion Rodriguez 6 ; Belmonte, Juan Carlos Izpisua 6 ; Yi, Fei 7 ; Suzuki, Keiichiro 8 ; Gao, Hua 9 ; Zhang, Chuanbao 10 ; Wang, Xiaomin 10 ; Jiang, Tao 10 ; Liu, Guang-Hui 10 ; Chen, Zhiguo 11 ; Tang, Fuchou 12 ; Tang, Fuchou 13 ; Liu, Guang-Hui 13 ; Tang, Fuchou 14 ;
Institute: 1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.; 2.Peking Univ, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China.; 3.FSU CAS Innovat Inst, Foshan 528000, Peoples R China.; 4.Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China.; 5.Univ Iowa, Dept Pathol, Carver Coll Med, Iowa City, IA 52242 USA.; 6.Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.; 7.Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA.; 8.Univ Catolica San Antonio Murcia UCAM, Murcia 30107, Spain.; 9.Tongji Univ, Shanghai East Hosp, Sch Life Sci & Technol, Res Ctr Translat Med, Shanghai 200092, Peoples R China.; 10.Beijing Inst Brain Disorders, Beijing 100069, Peoples R China.; 11.Capital Med Univ, Xuanwu Hosp, Cell Therapy Ctr, Beijing 100053, Peoples R China.; 12.Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China.; 13.CMTM, Beijing 100101, Peoples R China.; 14.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China.;


PTEN is a tumour suppressor frequently mutated in many types of cancers. Here we show that targeted disruption of PTEN leads to neoplastic transformation of human neural stem cells (NSCs), but not mesenchymal stem cells. PTEN-deficient NSCs display neoplasm-associated metabolic and gene expression profiles and generate intracranial tumours in immunodeficientmice. PTEN is localized to the nucleus in NSCs, binds to the PAX7 promoter through association with cAMP responsive element binding protein 1 (CREB)/CREB binding protein (CBP) and inhibits PAX7 transcription. PTEN deficiency leads to the upregulation of PAX7, which in turn promotes oncogenic transformation of NSCs and instates 'aggressiveness' in human glioblastoma stem cells. In a large clinical database, we find increased PAX7 levels in PTEN-deficient glioblastoma. Furthermore, we identify that mitomycin C selectively triggers apoptosis in NSCs with PTEN deficiency. Together, we uncover a potential mechanism of how PTEN safeguards NSCs, and establish a cellular platform to identify factors involved in NSC transformation, potentially permitting personalized treatment of glioblastoma.
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Recommended references: Duan, Shunlei,Yuan, Guohong,Ren, Ruotong,Xu, Xiuling,Fu, Lina,Li, Ying,Yang, Jiping,Zhang, Weiqi,Liu, Guang-Hui,Liu, Xiaomeng,Li, Jingyi,Tang, Fuchou,Ren, Ruotong,Bai, Ruijun,Liu, Guang-Hui,Ren, Ruotong,Bai, Ruijun,Qu, Jing,Zhang, Weizhou,Wu, Jun,Suzuki, Keiichiro,Esteban, Concepcion Rodriguez,Belmonte, Juan Carlos Izpisua,Yi, Fei,Suzuki, Keiichiro,Gao, Hua,Zhang, Chuanbao,Wang, Xiaomin,Jiang, Tao,Liu, Guang-Hui,Chen, Zhiguo,Tang, Fuchou,Tang, Fuchou,Liu, Guang-Hui,Tang, Fuchou.(2016).PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype.NATURE COMMUNICATIONS.[ChinaXiv:201605.01735] (Click&Copy)
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[V1] 2016-05-15 13:34:22 chinaXiv:201605.01735V1 Download
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