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

Autor: Aiala Lorente-Trigos, Marie Zbinden, Isabel Borges, Ariel Ruiz i Altaba, Sandra-Nadia Ngwabyt, Arnaud Duquet
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Homeobox protein NANOG
Male
Have You Seen...?
animal structures
Rex1
Cell
Bioinformatics
Zinc Finger Protein GLI1
Article
General Biochemistry
Genetics and Molecular Biology
Tumor Suppressor Protein p53/*metabolism
GLI1
medicine
Homeodomain Proteins/genetics/*metabolism
Tumor Cells
Cultured
Animals
Humans
ddc:576.5
Molecular Biology
Transcription Factors/*metabolism
reproductive and urinary physiology
Aged
Cell Proliferation
Homeodomain Proteins
Aged
80 and over
General Immunology and Microbiology
biology
integumentary system
Cell growth
General Neuroscience
Nanog Homeobox Protein
Glioma
Middle Aged
Glioma/*metabolism/pathology
Embryonic stem cell
Neoplastic Stem Cells/cytology/*metabolism
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
embryonic structures
Neoplastic Stem Cells
biology.protein
Cancer research
Female
Tumor Suppressor Protein p53
Stem cell
biological phenomena
cell phenomena
and immunity
Transcription Factors
Signal Transduction
Zdroj: EMBO Journal, Vol. 29, No 15 (2010) pp. 2659-2674
ISSN: 0261-4189
Popis: 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.
Databáze: OpenAIRE
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