RT Journal Article
SR Electronic
T1 Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesis
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800218
DO 10.26508/lsa.201800218
VO 2
IS 2
A1 Gabrielle V Rushing
A1 Asa A Brockman
A1 Madelyn K Bollig
A1 Nalin Leelatian
A1 Bret C Mobley
A1 Jonathan M Irish
A1 Kevin C Ess
A1 Cary Fu
A1 Rebecca A Ihrie
YR 2019
UL https://www.life-science-alliance.org/content/2/2/e201800218.abstract
AB 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.