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EMBO J. 2010 Aug 4;29(15):2659-74. doi: 10.1038/emboj.2010.137. Epub 2010 Jun 25.

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

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1
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.

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.

PMID:
20581802
PMCID:
PMC2928692
DOI:
10.1038/emboj.2010.137
[Indexed for MEDLINE]
Free PMC Article
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