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 Sci Alliance. 2019 2 (2)

PMID: 30910807 · PMCID: PMC6435042 · DOI:10.26508/lsa.201800218

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.

© 2019 Rushing et al.

MeSH Terms (19)

Adolescent Animals Astrocytoma Carcinogenesis Cells, Cultured Child Child, Preschool Disease Susceptibility Female Humans Lateral Ventricles Male Mechanistic Target of Rapamycin Complex 1 Mice Mice, Inbred C57BL Neural Stem Cells Signal Transduction Thyroid Nuclear Factor 1 Tuberous Sclerosis

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