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

Lorente-Trigos, Aiala
Ngwabyt, Sandra-Nadia
Borges, Isabel
Published in EMBO Journal. 2010, vol. 29, no. 15, p. 2659-2674
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 AgedAged, 80 and overAnimalsCell ProliferationFemaleGene Expression Regulation, NeoplasticGlioma/*metabolism/pathologyHomeodomain Proteins/genetics/*metabolismHumansMaleMiddle AgedNeoplastic Stem Cells/cytology/*metabolismSignal TransductionTranscription Factors/*metabolismTumor Cells, CulturedTumor Suppressor Protein p53/*metabolism
PMID: 20581802
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Research group Stemness dans le développement et les maladies: Signalisation, reprogrammation et mécanismes des métastases (776)
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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. https://archive-ouverte.unige.ch/unige:21402

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Deposited on : 2012-05-23

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