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

doi:10.1038/ncomms10068

CORC > 北京大学 > 生命科学学院

	PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype
	Duan, Shunlei ; Yuan, Guohong ; Liu, Xiaomeng ; Ren, Ruotong ; Li, Jingyi ; Zhang, Weizhou ; Wu, Jun ; Xu, Xiuling ; Fu, Lina ; Li, Ying ; Yang, Jiping ; Zhang, Weiqi ; Bai, Ruijun ; Yi, Fei ; Suzuki, Keiichiro ; Gao, Hua ; Esteban, Concepcion Rodriguez ; Zhang, Chuanbao ; Belmonte, Juan Carlos Izpisua ; Chen, Zhiguo ; Wang, Xiaomin ; Jiang, Tao ; Qu, Jing ; Tang, Fuchou ; Liu, Guang-Hui
刊名	NATURE COMMUNICATIONS
	2015
关键词	MALIGNANT ASTROCYTIC GLIOMA TUMOR-INITIATING CELLS RNA-SEQ STEM/PROGENITOR CELLS KINASE INHIBITORS SELF-RENEWAL MOUSE MODELS HUMAN BRAIN CANCER GENE
DOI	10.1038/ncomms10068
英文摘要	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.; National Basic Research Program of China 973 Program [2015CB964800, 2014CB910503, 2014CB964600, 2012CB966704, 2011CB504100]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA01020312]; Beijing Natural Science Foundation [7141005, 5142016]; National High Technology Research and Development Program of China [2015AA020307]; National Natural Science Foundation of China (NSFC) [81330008, 31222039, 31201111, 81371342, 81300261, 81300677, 81271266, 81471414, 81422017, 81401159, 31322039]; Program of Beijing Municipal Science and Technology Commission [Z151100003915072]; Chinese Academy of Sciences [KJZDEW-TZ-L05]; Thousand Young Talents program of China, National Laboratory of Biomacromolecules [012kf02, 2013kf05, 2013kf11, 2014kf02, 2015kf10]; State Key Laboratory of Drug Research [SIMM1302KF-17]; China Postdoctoral Science Foundation Grant [2013M530751]; Salk Institute Cancer Center Support Grant, Universidad Catolica San Antonio de Murcia (UCAM); G. Harold and Leila Y. Mathers Charitable Foundation; Leona M. and Harry B. Helmsley Charitable Trust [PG-2012-MED002]; NIH [K99/R00 CA158055]; Holden Comprehensive Cancer Center at the University of Iowa [P30CA086862]; Department of Pathology, University of Iowa; SCI(E); PubMed; ARTICLE; qujing@ioz.ac.cn; tangfuchou@pku.edu.cn; ghliu@ibp.ac.cn; 10068; 6
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/436012]
专题	生命科学学院
推荐引用方式 GB/T 7714	Duan, Shunlei,Yuan, Guohong,Liu, Xiaomeng,et al. PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype[J]. NATURE COMMUNICATIONS,2015.
APA	Duan, Shunlei.,Yuan, Guohong.,Liu, Xiaomeng.,Ren, Ruotong.,Li, Jingyi.,...&Liu, Guang-Hui.(2015).PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype.NATURE COMMUNICATIONS.
MLA	Duan, Shunlei,et al."PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype".NATURE COMMUNICATIONS (2015).