title: mTORC2 in the center of cancer metabolic reprogramming.
abstract: Metabolic reprogramming is a central hallmark of cancer, enabling tumor cells to obtain the macromolecular precursors and energy needed for rapid tumor growth. Understanding how oncogenes coordinate altered signaling with metabolic reprogramming and global transcription may yield new insights into tumor pathogenesis, and provide a new landscape of promising drug targets, while yielding important clues into mechanisms of resistance to the signal transduction inhibitors currently in use. We review here the recently identified central regulatory role for mechanistic target of rapamycin complex 2 (mTORC2), a downstream effector of many cancer-causing mutations, in metabolic reprogramming and cancer drug resistance. We consider the impact of mTORC2-related metabolism on epigenetics and therapeutics, with a particular focus on the intractable malignant brain tumor, glioblastoma multiforme (GBM).
authors.affiliation: Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, USA; Laboratory of Neuropathology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Masui
authors.affiliation: Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92093, 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 92093, USA. Electronic address: pmischel@ucsd.edu.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Mischel
mesh_terms: D000818:Animals; D057890:Epigenomics; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; 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: c-Myc; drug resistance; epigenetics; glioblastoma; mTORC2; metabolic reprogramming