@article{RN6120,
   author = {Shingu, T. and Ho, A. L. and Yuan, L. and Zhou, X. and Dai, C. and Zheng, S. and Wang, Q. and Zhong, Y. and Chang, Q. and Horner, J. W. and Liebelt, B. D. and Yao, Y. and Hu, B. and Chen, Y. and Fuller, G. N. and Verhaak, R. G. and Heimberger, A. B. and Hu, J.},
   title = {Qki deficiency maintains stemness of glioma stem cells in suboptimal environment by downregulating endolysosomal degradation},
   journal = {Nat Genet},
   volume = {49},
   number = {1},
   pages = {75-86},
   note = {1546-1718
Shingu, Takashi
Ho, Allen L
Yuan, Liang
Zhou, Xin
Dai, Congxin
Zheng, Siyuan
Orcid: 0000-0002-1031-9424
Wang, Qianghu
Zhong, Yi
Chang, Qing
Horner, James W
Liebelt, Brandon D
Orcid: 0000-0001-8707-9329
Yao, Yu
Hu, Baoli
Chen, Yiwen
Fuller, Gregory N
Verhaak, Roeland G W
Heimberger, Amy B
Hu, Jian
R01 CA120813/CA/NCI NIH HHS/United States
P30 CA016672/CA/NCI NIH HHS/United States
HHMI/Howard Hughes Medical Institute/United States
R00 CA172700/CA/NCI NIH HHS/United States
R00 CA175290/CA/NCI NIH HHS/United States
P50 CA127001/CA/NCI NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
United States
2016/11/15
Nat Genet. 2017 Jan;49(1):75-86. doi: 10.1038/ng.3711. Epub 2016 Nov 14.},
   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-CreER(T2); Qk(L/L); Pten(L/L); Trp53(L/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.},
   keywords = {Animals
Brain Neoplasms/genetics/metabolism/*pathology
Cells, Cultured
Endosomes/*metabolism
Female
Glioma/genetics/metabolism/*pathology
Lysosomes/*metabolism
Mice
Mice, Knockout
Mice, Nude
Mice, SCID
Neoplastic Stem Cells/metabolism/*pathology
Neural Stem Cells/metabolism/*pathology
PTEN Phosphohydrolase/physiology
Proteolysis
RNA-Binding Proteins/*physiology
Receptors, Cell Surface/metabolism
Stem Cell Niche
Tumor Suppressor Protein p53/physiology},
   ISSN = {1061-4036 (Print)
1061-4036},
   DOI = {10.1038/ng.3711},
   year = {2017},
   type = {Journal Article}
}

{"_id":"yxSi3hfbStpfsmb8G","bibbaseid":"shingu-ho-yuan-zhou-dai-zheng-wang-zhong-etal-qkideficiencymaintainsstemnessofgliomastemcellsinsuboptimalenvironmentbydownregulatingendolysosomaldegradation-2017","authorIDs":["5dce3b23dcea22df0100007c","5dec52fce16431f2010000c9","5dec5944e16431f2010000fa","5e0a5e7ace3ebce40100010e","5e2ff5be5bfc8ede0100003b","c8zrScQz6casKGL4t"],"author_short":["Shingu, T.","Ho, A. L.","Yuan, L.","Zhou, X.","Dai, C.","Zheng, S.","Wang, Q.","Zhong, Y.","Chang, Q.","Horner, J. W.","Liebelt, B. D.","Yao, Y.","Hu, B.","Chen, Y.","Fuller, G. N.","Verhaak, R. G.","Heimberger, A. B.","Hu, J."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Shingu"],"firstnames":["T."],"suffixes":[]},{"propositions":[],"lastnames":["Ho"],"firstnames":["A.","L."],"suffixes":[]},{"propositions":[],"lastnames":["Yuan"],"firstnames":["L."],"suffixes":[]},{"propositions":[],"lastnames":["Zhou"],"firstnames":["X."],"suffixes":[]},{"propositions":[],"lastnames":["Dai"],"firstnames":["C."],"suffixes":[]},{"propositions":[],"lastnames":["Zheng"],"firstnames":["S."],"suffixes":[]},{"propositions":[],"lastnames":["Wang"],"firstnames":["Q."],"suffixes":[]},{"propositions":[],"lastnames":["Zhong"],"firstnames":["Y."],"suffixes":[]},{"propositions":[],"lastnames":["Chang"],"firstnames":["Q."],"suffixes":[]},{"propositions":[],"lastnames":["Horner"],"firstnames":["J.","W."],"suffixes":[]},{"propositions":[],"lastnames":["Liebelt"],"firstnames":["B.","D."],"suffixes":[]},{"propositions":[],"lastnames":["Yao"],"firstnames":["Y."],"suffixes":[]},{"propositions":[],"lastnames":["Hu"],"firstnames":["B."],"suffixes":[]},{"propositions":[],"lastnames":["Chen"],"firstnames":["Y."],"suffixes":[]},{"propositions":[],"lastnames":["Fuller"],"firstnames":["G.","N."],"suffixes":[]},{"propositions":[],"lastnames":["Verhaak"],"firstnames":["R.","G."],"suffixes":[]},{"propositions":[],"lastnames":["Heimberger"],"firstnames":["A.","B."],"suffixes":[]},{"propositions":[],"lastnames":["Hu"],"firstnames":["J."],"suffixes":[]}],"title":"Qki deficiency maintains stemness of glioma stem cells in suboptimal environment by downregulating endolysosomal degradation","journal":"Nat Genet","volume":"49","number":"1","pages":"75-86","note":"1546-1718 Shingu, Takashi Ho, Allen L Yuan, Liang Zhou, Xin Dai, Congxin Zheng, Siyuan Orcid: 0000-0002-1031-9424 Wang, Qianghu Zhong, Yi Chang, Qing Horner, James W Liebelt, Brandon D Orcid: 0000-0001-8707-9329 Yao, Yu Hu, Baoli Chen, Yiwen Fuller, Gregory N Verhaak, Roeland G W Heimberger, Amy B Hu, Jian R01 CA120813/CA/NCI NIH HHS/United States P30 CA016672/CA/NCI NIH HHS/United States HHMI/Howard Hughes Medical Institute/United States R00 CA172700/CA/NCI NIH HHS/United States R00 CA175290/CA/NCI NIH HHS/United States P50 CA127001/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States 2016/11/15 Nat Genet. 2017 Jan;49(1):75-86. doi: 10.1038/ng.3711. Epub 2016 Nov 14.","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-CreER(T2); Qk(L/L); Pten(L/L); Trp53(L/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.","keywords":"Animals Brain Neoplasms/genetics/metabolism/*pathology Cells, Cultured Endosomes/*metabolism Female Glioma/genetics/metabolism/*pathology Lysosomes/*metabolism Mice Mice, Knockout Mice, Nude Mice, SCID Neoplastic Stem Cells/metabolism/*pathology Neural Stem Cells/metabolism/*pathology PTEN Phosphohydrolase/physiology Proteolysis RNA-Binding Proteins/*physiology Receptors, Cell Surface/metabolism Stem Cell Niche Tumor Suppressor Protein p53/physiology","issn":"1061-4036 (Print) 1061-4036","doi":"10.1038/ng.3711","year":"2017","bibtex":"@article{RN6120,\n author = {Shingu, T. and Ho, A. L. and Yuan, L. and Zhou, X. and Dai, C. and Zheng, S. and Wang, Q. and Zhong, Y. and Chang, Q. and Horner, J. W. and Liebelt, B. D. and Yao, Y. and Hu, B. and Chen, Y. and Fuller, G. N. and Verhaak, R. G. and Heimberger, A. B. and Hu, J.},\n title = {Qki deficiency maintains stemness of glioma stem cells in suboptimal environment by downregulating endolysosomal degradation},\n journal = {Nat Genet},\n volume = {49},\n number = {1},\n pages = {75-86},\n note = {1546-1718\nShingu, Takashi\nHo, Allen L\nYuan, Liang\nZhou, Xin\nDai, Congxin\nZheng, Siyuan\nOrcid: 0000-0002-1031-9424\nWang, Qianghu\nZhong, Yi\nChang, Qing\nHorner, James W\nLiebelt, Brandon D\nOrcid: 0000-0001-8707-9329\nYao, Yu\nHu, Baoli\nChen, Yiwen\nFuller, Gregory N\nVerhaak, Roeland G W\nHeimberger, Amy B\nHu, Jian\nR01 CA120813/CA/NCI NIH HHS/United States\nP30 CA016672/CA/NCI NIH HHS/United States\nHHMI/Howard Hughes Medical Institute/United States\nR00 CA172700/CA/NCI NIH HHS/United States\nR00 CA175290/CA/NCI NIH HHS/United States\nP50 CA127001/CA/NCI NIH HHS/United States\nJournal Article\nResearch Support, N.I.H., Extramural\nResearch Support, Non-U.S. Gov't\nUnited States\n2016/11/15\nNat Genet. 2017 Jan;49(1):75-86. doi: 10.1038/ng.3711. Epub 2016 Nov 14.},\n 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-CreER(T2); Qk(L/L); Pten(L/L); Trp53(L/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.},\n keywords = {Animals\nBrain Neoplasms/genetics/metabolism/*pathology\nCells, Cultured\nEndosomes/*metabolism\nFemale\nGlioma/genetics/metabolism/*pathology\nLysosomes/*metabolism\nMice\nMice, Knockout\nMice, Nude\nMice, SCID\nNeoplastic Stem Cells/metabolism/*pathology\nNeural Stem Cells/metabolism/*pathology\nPTEN Phosphohydrolase/physiology\nProteolysis\nRNA-Binding Proteins/*physiology\nReceptors, Cell Surface/metabolism\nStem Cell Niche\nTumor Suppressor Protein p53/physiology},\n ISSN = {1061-4036 (Print)\n1061-4036},\n DOI = {10.1038/ng.3711},\n year = {2017},\n type = {Journal Article}\n}\n\n","author_short":["Shingu, T.","Ho, A. L.","Yuan, L.","Zhou, X.","Dai, C.","Zheng, S.","Wang, Q.","Zhong, Y.","Chang, Q.","Horner, J. W.","Liebelt, B. D.","Yao, Y.","Hu, B.","Chen, Y.","Fuller, G. N.","Verhaak, R. 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