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Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesis


Rushing GV , Brockman AA , Bollig MK , Leelatian N , Mobley BC , Irish JM , Ess KC , Fu C , Ihrie RA , . Life science alliance. 2019 3 25; 2(2).


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 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.