title: Qki deficiency maintains stemness of glioma stem cells in suboptimal environment by downregulating endolysosomal degradation.
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/Lmice, 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.
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shingu
authors.affiliation: Department of Neurosurgery, Stanford University, Stanford, California, USA.
authors.forename: Allen L
authors.initials: AL
authors.lastname: Ho
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Congxin
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Siyuan
authors.identifier: 0000-0002-1031-9424
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Qianghu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Horner
authors.affiliation: Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Neurosurgery, Houston Methodist Neurological Institute, Houston, Texas, USA.
authors.forename: Brandon D
authors.identifier: 0000-0001-8707-9329
authors.initials: BD
authors.lastname: Liebelt
authors.affiliation: Department of Neurosurgery, Fudan University Huashan Hospital, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Baoli
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.affiliation: Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Roeland G W
authors.initials: RG
authors.lastname: Verhaak
authors.affiliation: Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000502:physiology; D059748:Proteolysis; D016601:RNA-Binding Proteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D055153:Stem Cell Niche; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: C098217:Qk protein, mouse; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse