Journal article
PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype
Nature communications, Vol.6(1), pp.10068-10068
12/03/2015
DOI: 10.1038/ncomms10068
PMCID: PMC4686761
PMID: 26632666
Abstract
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 immunodeficient mice. 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.
Details
- Title: Subtitle
- PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype
- Creators
- Shunlei Duan - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaGuohong Yuan - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaXiaomeng Liu - Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, ChinaRuotong Ren - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, ChinaJingyi Li - Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, ChinaWeizhou Zhang - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USAJun Wu - Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USAXiuling Xu - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaLina Fu - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaYing Li - Chinese Academy of SciencesJiping Yang - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaWeiqi Zhang - National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, ChinaRuijun Bai - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, ChinaFei Yi - Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USAKeiichiro Suzuki - Universidad Católica San Antonio de Murcia (UCAM) Campus de los Jerónimos, No 135 Guadalupe, 30107 Murcia, SpainHua Gao - Research Center for Translational Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaConcepcion Rodriguez Esteban - Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USAChuanbao Zhang - Beijing Institute for Brain Disorders, Beijing 100069, ChinaJuan Carlos Izpisua Belmonte - Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USAZhiguo Chen - Cell Therapy Center, Xuanwu Hospital Capital Medical University, Beijing 100053, ChinaXiaomin Wang - Beijing Institute for Brain Disorders, Beijing 100069, ChinaTao Jiang - Beijing Institute for Brain Disorders, Beijing 100069, ChinaJing Qu - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, ChinaFuchou Tang - Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, ChinaGuang-Hui Liu - Center for Molecular and Translational Medicine, CMTM, Beijing 100101, China
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.6(1), pp.10068-10068
- DOI
- 10.1038/ncomms10068
- PMID
- 26632666
- PMCID
- PMC4686761
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- R00 CA158055 / NCI NIH HHS P30 CA014195 / NCI NIH HHS K99 CA158055 / NCI NIH HHS K99/R00 CA158055 / NCI NIH HHS P30CA086862 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 12/03/2015
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984083289802771
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