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Nat Genet. 2017 Jan;49(1):75-86. doi: 10.1038/ng.3711. Epub 2016 Nov 14.

Qki deficiency maintains stemness of glioma stem cells in suboptimal environment by downregulating endolysosomal degradation.

Author information

1
Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
2
Department of Neurosurgery, Stanford University, Stanford, California, USA.
3
Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
4
Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
5
Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
6
Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
7
Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
8
Department of Neurosurgery, Houston Methodist Neurological Institute, Houston, Texas, USA.
9
Department of Neurosurgery, Fudan University Huashan Hospital, Shanghai, China.
10
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Abstract

Stem cells, including cancer stem cells (CSCs), require niches to maintain stemness, yet it is unclear how CSCs maintain stemness in the suboptimal environment outside their niches during invasion. Postnatal co-deletion of Pten and Trp53 in mouse neural stem cells (NSCs) leads to the expansion of these cells in their subventricular zone (SVZ) niches but fails to maintain stemness outside the SVZ. We discovered that Qki is a major regulator of NSC stemness. Qk deletion on a Pten-/-; Trp53-/- background helps NSCs maintain their stemness outside the SVZ in Nes-CreERT2; QkL/L; PtenL/L; Trp53L/L mice, which develop glioblastoma with a penetrance of 92% and a median survival time of 105 d. Mechanistically, Qk deletion decreases endolysosome-mediated degradation and enriches receptors essential for maintaining self-renewal on the cytoplasmic membrane to cope with low ligand levels outside niches. Thus, downregulation of endolysosome levels by Qki loss helps glioma stem cells (GSCs) maintain their stemness in suboptimal environments outside their niches.

PMID:
27841882
PMCID:
PMC5453714
DOI:
10.1038/ng.3711
[Indexed for MEDLINE]
Free PMC Article

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