机构：[1]National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.[2]Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.[3]FSU-CAS Innovation Institute, Foshan 528000, China.[4]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.[5]Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.[6]Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.[7]Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.[8]Universidad Cato′lica San Antonio de Murcia (UCAM) Campus de los Jero′nimos, No 135 Guadalupe, 30107 Murcia, Spain.[9]Research Center for Translational Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.[10]Beijing Institute for Brain Disorders, Beijing 100069, China.[11]Cell Therapy Center, Xuanwu Hospital Capital Medical University, Beijing 100053, China.首都医科大学宣武医院[12]Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.[13]Center for Molecular and Translational Medicine, CMTM, Beijing 100101, China.[14]Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, 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.
基金：
the National Basic Research Program of China (973 Program, 2015CB964800;2014CB910503; 2014CB964600; 2012CB966704;2011CB504100),
the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01020312),
the Beijing Natural Science Foundation (7141005; 5142016),
the National High Technology Research and Development Program of China(2015AA020307),
the National Natural Science Foundation of China (NSFC: 81330008;
31222039; 31201111; 81371342; 81300261; 81300677; 81271266; 81471414; 81422017;81401159; 31322039),
the Program of Beijing Municipal Science and Technology Commission (Z151100003915072),
the Key Research Program of the Chinese Academy of Sciences (KJZDEW-TZ-L05),
the Thousand Young Talents program of China, National Laboratory of Biomacromolecules (012kf02;2013kf05;2013kf11;2014kf02;2015kf10),
the State Key Laboratory of Drug Research (SIMM1302KF-17)
the China Postdoctoral Science Foundation Grant (2013M530751).
the Salk Institute Cancer Center Support Grant, Universidad Cato′lica San Antonio de Murcia (UCAM),
the G. Harold and Leila Y. Mathers Charitable Foundation
the Leona M. and Harry B. Helmsley Charitable Trust (PG-2012-MED002).
NIH grants K99/R00 CA158055,
the V Scholar award, American Cancer Society seed grant,
Breast Cancer Research Award and Oberley Award (National Cancer Institute Award P30CA086862)
from Holden Comprehensive Cancer Center at the University of Iowa,
startup funds from the Department of Pathology, University of Iowa.
第一作者机构：[1]National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
共同第一作者：
通讯作者：
通讯机构：[1]National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.[2]Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.[3]FSU-CAS Innovation Institute, Foshan 528000, China.[4]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.[10]Beijing Institute for Brain Disorders, Beijing 100069, China.[12]Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.[13]Center for Molecular and Translational Medicine, CMTM, Beijing 100101, China.[14]Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
推荐引用方式(GB/T 7714)：
Shunlei Duan,Guohong Yuan,Xiaomeng Liu,et al.PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype[J].NATURE COMMUNICATIONS.2015,6:doi:10.1038/ncomms10068.
APA：
Shunlei Duan,Guohong Yuan,Xiaomeng Liu,Ruotong Ren,Jingyi Li...&Guang-Hui Liu.(2015).PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype.NATURE COMMUNICATIONS,6,
MLA：
Shunlei Duan,et al."PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype".NATURE COMMUNICATIONS 6.(2015)
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