title: mTORC2 activity in brain cancer: Extracellular nutrients are required to maintain oncogenic signaling.
abstract: Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro-environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin complex 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies.
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Masui
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, USA.
authors.forename: Webster K
authors.initials: WK
authors.lastname: Cavenee
authors.affiliation: Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Mischel
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism*; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases
keywords: genetic-environment interaction; genetics; glioblastoma; mTOR; metabolic reprogramming