title: mTORC1 and mTORC2 in cancer and the tumor microenvironment.
abstract: The mammalian target of rapamycin (mTOR) is a crucial signaling node that integrates environmental cues to regulate cell survival, proliferation and metabolism, and is often deregulated in human cancer. mTOR kinase acts in two functionally distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), whose activities and substrate specificities are regulated by complex co-factors. Deregulation of this centralized signaling pathway has been associated with a variety of human diseases including diabetes, neurodegeneration and cancer. Although mTORC1 signaling has been extensively studied in cancer, recent discoveries indicate a subset of human cancers harboring amplifications in mTORC2-specific genes as the only actionable genomic alterations, suggesting a distinct role for mTORC2 in cancer as well. This review will summarize recent advances in dissecting the relative contributions of mTORC1 versus mTORC2 in cancer, their role in tumor-associated blood vessels and tumor immunity, and provide an update on mTOR inhibitors.
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Kim
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Cook
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.|Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University, Nashville, TN, USA.|Department of Cell & Developmental Biology, Vanderbilt University, Nashville, TN, USA.|Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases