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Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth.
Hu, Baoli; Wang, Qianghu; Wang, Y Alan; Hua, Sujun; Sauvé, Charles-Etienne Gabriel; Ong, Derrick; Lan, Zheng D; Chang, Qing; Ho, Yan Wing; Monasterio, Marta Moreno; Lu, Xin; Zhong, Yi; Zhang, Jianhua; Deng, Pingna; Tan, Zhi; Wang, Guocan; Liao, Wen-Ting; Corley, Lynda J; Yan, Haiyan; Zhang, Junxia; You, Yongping; Liu, Ning; Cai, Linbo; Finocchiaro, Gaetano; Phillips, Joanna J; Berger, Mitchel S; Spring, Denise J; Hu, Jian; Sulman, Erik P; Fuller, Gregory N; Chin, Lynda; Verhaak, Roeland G W; DePinho, Ronald A.
Afiliación
  • Hu B; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Wang Q; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Wang YA; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: yalanwang@mdanderson.org.
  • Hua S; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Sauvé CG; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ong D; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lan ZD; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chang Q; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ho YW; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Monasterio MM; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lu X; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zhong Y; Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zhang J; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Deng P; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Tan Z; Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Wang G; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Liao WT; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Corley LJ; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Yan H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Zhang J; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • You Y; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Liu N; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Cai L; Department of Oncology, Guangdong 999 Brain Hospital, Guangzhou 510510, China.
  • Finocchiaro G; Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico C. Besta, 20133 Milano, Italy.
  • Phillips JJ; Departments of Neurological Surgery and Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Berger MS; Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Spring DJ; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Hu J; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Sulman EP; Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Fuller GN; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Chin L; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Verhaak RGW; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • DePinho RA; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: rdepinho@mdanderson.org.
Cell ; 167(5): 1281-1295.e18, 2016 11 17.
Article en En | MEDLINE | ID: mdl-27863244
ABSTRACT
Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, we developed a de novo glioblastoma multiforme (GBM) model derived from immortalized human neural stem/progenitor cells (hNSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells (GdECs). GdECs recruit existing endothelial cells to promote peritumoral satellite lesions, which serve as a niche supporting the growth of invasive glioma cells away from the primary tumor. Clinical data reveal higher WNT5A and GdECs expression in peritumoral and recurrent GBMs relative to matched intratumoral and primary GBMs, respectively, supporting WNT5A-mediated GSC differentiation and invasive growth in disease recurrence. Thus, the PAX6/DLX5-WNT5A axis governs the diffuse spread of glioma cells throughout the brain parenchyma, contributing to the lethality of GBM.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Glioblastoma / Proteína Wnt-5a / Invasividad Neoplásica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Glioblastoma / Proteína Wnt-5a / Invasividad Neoplásica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos