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NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53
Article first published online: 25 JUN 2010
Copyright © 2010 European Molecular Biology Organization
The EMBO Journal
Volume 29, Issue 15, pages 2659–2674, August 4, 2010
How to Cite
Zbinden, M., Duquet, A., Lorente-Trigos, A., Ngwabyt, S.-N., Borges, I. and Ruiz i Altaba, A. (2010), NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53. The EMBO Journal, 29: 2659–2674. doi: 10.1038/emboj.2010.137
- Issue published online: 4 AUG 2010
- Article first published online: 25 JUN 2010
- Manuscript Accepted: 2 JUN 2010
- Manuscript Received: 2 MAR 2010
- stem cell
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.