Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesis
Year: 2019
Type: article
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 pathognomonicTsc2mutation 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.
Source: Life Science Alliance
Institutions: Vanderbilt University, Vanderbilt University Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funders: U.S. Department of Defense, Tuberous Sclerosis Alliance, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, National Institutes of Health, Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center, National Eye Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1002678292, G107554336, G1149166549, G1300984159, G1344704808, G153582612, G179951968, G2007021101, G2019238319, IDENTIFYING NOVEL CANDIDATE THERAPIES FOR SEGAS USING QUANTITATIVE SINGLE-CELL ASSAYS, G2268269956, G2304076072, G256475304, Leica Bond RX, G275963511, G2815659365, Vanderbilt Mouse Metabolic Phenotyping Center, G3416501184, G3433274139, G344109072, G3615027464, G3726302789, G3756376927, G3855720138, G3865556588, G3977540851, Vanderbilt Mouse Metabolic Phenotyping Center, G4119534169, G4320917349, G4416941928, G4513176822, LSM880-Airyscan Confocal Microscope for Large Shared Resource, Cancer Center Support Grant, G5132347646, G5850682332, G5853943267, G6297262231, G6546324823, Regulation of Neurogenesis in TSC by mTORC1 and mTORC2, G7220527126, G725763919, G7520984233, G8225207124, G8410895666, Diabetes Research and Training Center, G8486071729, G8953775245, G9000002043, G9000060478, G9000076948, G9000081609, G9000083539, G9000089795, G9000106052, G9000130510, G9000159340, Molecular and Cellular Basis for Digestive Diseases, Vanderbilt Diabetes Research Center, Core Grant in Vision Research, G903003502
OpenAlex ID: W2928252176