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Scientific article
English

NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53

Published inEMBO journal, vol. 29, no. 15, p. 2659-2674
Publication date2010
Abstract

A cohort of genes associated with embryonic stem (ES) cell behaviour, including NANOG, are expressed in a number of human cancers. They form an ES-like signature we first described in glioblastoma multiforme (GBM), a highly invasive and incurable brain tumour. We have also shown that HEDGEHOG-GLI (HH-GLI) signalling is required for GBM growth, stem cell expansion and the expression of this (ES)-like stemness signature. Here, we address the function of NANOG in human GBMs and its relationship with HH-GLI activity. We find that NANOG modulates gliomasphere clonogenicity, CD133(+) stem cell cell behavior and proliferation, and is regulated by HH-GLI signalling. However, GLI1 also requires NANOG activity forming a positive loop, which is negatively controlled by p53 and vice versa. NANOG is essential for GBM tumourigenicity in orthotopic xenografts and it is epistatic to HH-GLI activity. Our data establish NANOG as a novel HH-GLI mediator essential for GBMs. We propose that this function is conserved and that tumour growth and stem cell behaviour rely on the status of a functional GLI1-NANOG-p53 network.

Keywords
  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma/*metabolism/pathology
  • Homeodomain Proteins/genetics/*metabolism
  • Humans
  • Male
  • Middle Aged
  • Neoplastic Stem Cells/cytology/*metabolism
  • Signal Transduction
  • Transcription Factors/*metabolism
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53/*metabolism
Citation (ISO format)
ZBINDEN, Marie et al. NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53. In: EMBO journal, 2010, vol. 29, n° 15, p. 2659–2674. doi: 10.1038/emboj.2010.137
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ISSN of the journal0261-4189
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