title: Metabolic Reprogramming by the PI3K-Akt-mTOR Pathway in Cancer.
abstract: In the past decade, there has been a resurgence of interest in elucidating how metabolism is altered in cancer cells and how such dependencies can be targeted for therapeutic gain. At the core of this research is the concept that metabolic pathways are reprogrammed in cancer cells to divert nutrients toward anabolic processes to facilitate enhanced growth and proliferation. Importantly, physiological cellular signaling mechanisms normally tightly regulate the ability of cells to gain access to and utilize nutrients, posing a fundamental barrier to transformation. This barrier is often overcome by aberrations in cellular signaling that drive tumor pathogenesis by enabling cancer cells to make critical cellular decisions in a cell-autonomous manner. One of the most frequently altered pathways in human cancer is the PI3K-Akt-mTOR signaling pathway. Here, we describe mechanisms by which this signaling network is responsible for controlling cellular metabolism. Through both the post-translational regulation and the induction of transcriptional programs, the PI3K-Akt-mTOR pathway coordinates the uptake and utilization of multiple nutrients, including glucose, glutamine, nucleotides, and lipids, in a manner best suited for supporting the enhanced growth and proliferation of cancer cells. These regulatory mechanisms illustrate how metabolic changes in cancer are closely intertwined with oncogenic signaling pathways that drive tumor initiation and progression.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, EC/CLS-628C, Boston, MA, 02215, USA.
authors.forename: Evan C
authors.initials: EC
authors.lastname: Lien
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, 1150 E. Medical Center Drive, Room 6308, Ann Arbor, MI, 48109, USA.|Department of Internal Medicine, Division of Gastroenterology, University of Michigan, 1150 E. Medical Center Drive, Room 6308, Ann Arbor, MI, 48109, USA.
authors.forename: Costas A
authors.initials: CA
authors.lastname: Lyssiotis
authors.affiliation: Department of Medicine, the Cancer Center, Weill Cornell Medical College, The Belfer Research Building, 413 East 69th Street, Floor 13 Room BB-1362, New York, NY, 10021, USA. lcantley@med.cornell.edu.
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Cantley
mesh_terms: D063646:Carcinogenesis / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
keywords: Akt; Cancer; Metabolism; PI3K; Signaling; mTOR