title: Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton.
abstract: The phosphoinositide 3-kinase (PI3K) pathway regulates multiple steps in glucose metabolism and also cytoskeletal functions, such as cell movement and attachment. Here, we show that PI3K directly coordinates glycolysis with cytoskeletal dynamics in an AKT-independent manner. Growth factors or insulin stimulate the PI3K-dependent activation of Rac, leading to disruption of the actin cytoskeleton, release of filamentous actin-bound aldolase A, and an increase in aldolase activity. Consistently, PI3K inhibitors, but not AKT, SGK, or mTOR inhibitors, cause a significant decrease in glycolysis at the step catalyzed by aldolase, while activating PIK3CA mutations have the opposite effect. These results point toward a master regulatory function of PI3K that integrates an epithelial cell's metabolism and its form, shape, and function, coordinating glycolysis with the energy-intensive dynamics of actin remodeling.
authors.affiliation: Division of Hematology and Oncology, Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS), Boston, MA 02215, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Hu
authors.affiliation: Division of Hematology and Oncology, Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS), Boston, MA 02215, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Juvekar
authors.affiliation: Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
authors.forename: Costas A
authors.initials: CA
authors.lastname: Lyssiotis
authors.affiliation: Department of Pathology, BIDMC, Boston, MA 02215, USA.
authors.forename: Evan C
authors.initials: EC
authors.lastname: Lien
authors.affiliation: Department of Cell Biology, HMS, Boston, MA 02215, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Albeck
authors.affiliation: Department of Molecular and Cellular Biology, FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Doogie
authors.initials: D
authors.lastname: Oh
authors.affiliation: Department of Radiology, BIDMC Boston, MA 02215, USA.
authors.forename: Gopal
authors.initials: G
authors.lastname: Varma
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Yin Pun
authors.initials: YP
authors.lastname: Hung
authors.affiliation: Longwood Small Animal Imaging Facility, BIDMC, Boston, MA 02215, USA.
authors.forename: Soumya
authors.initials: S
authors.lastname: Ullas
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Josh
authors.initials: J
authors.lastname: Lauring
authors.affiliation: Division of Interdisciplinary Medicine, BIDMC, Boston, MA 02215, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.affiliation: Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Lundquist
authors.affiliation: Department of Biology, Boston University, Boston, MA 02215, USA.
authors.forename: Dean R
authors.initials: DR
authors.lastname: Tolan
authors.affiliation: Department of Radiology, BIDMC Boston, MA 02215, USA.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Grant
authors.affiliation: Department of Molecular and Cellular Biology, FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Needleman
authors.affiliation: Division of Signal Transduction, BIDMC, Boston, MA 02215, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Asara
authors.affiliation: Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Cantley
authors.affiliation: Division of Hematology and Oncology, Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS), Boston, MA 02215, USA. Electronic address: gwulf@bidmc.harvard.edu.
authors.forename: Gerburg M
authors.initials: GM
authors.lastname: Wulf
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction
chemical_list: D005634:Fructose-Bisphosphate Aldolase; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors
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