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Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven
Authors Rushing GV, Brockman AA, Bollig MK, Leelatian N, Mobley BC, Irish JM, Ess KC, Fu
C, Ihrie RA
Submitted By Submitted Externally on 4/8/2019
Status Published
Journal Life science alliance
Year 2019
Date Published 4/1/2019
Volume : Pages 2 : Not Specified
PubMed Reference 30910807
Abstract Neural stem/progenitor cells (NSPCs) of the ventricular-subventricular zone
(V-SVZ) are candidate cells of origin for many brain tumors. However, whether
NSPCs in different locations within the V-SVZ differ in susceptibility to
tumorigenic mutations is unknown. Here, single-cell measurements of signal
transduction intermediates in the mechanistic target of rapamycin complex 1
(mTORC1) pathway reveal that ventral NSPCs have higher levels of signaling than
dorsal NSPCs. These features are linked with differences in mTORC1-driven
disease severity: introduction of a pathognomonic Tsc2 mutation only results in
formation of tumor-like masses from the ventral V-SVZ. We propose a direct link
between location-dependent intrinsic growth properties imbued by mTORC1 and
predisposition to tumor development.


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