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Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton.
Hu, Hai; Juvekar, Ashish; Lyssiotis, Costas A; Lien, Evan C; Albeck, John G; Oh, Doogie; Varma, Gopal; Hung, Yin Pun; Ullas, Soumya; Lauring, Josh; Seth, Pankaj; Lundquist, Mark R; Tolan, Dean R; Grant, Aaron K; Needleman, Daniel J; Asara, John M; Cantley, Lewis C; Wulf, Gerburg M.
Affiliation
  • Hu H; Division of Hematology and Oncology, Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS), Boston, MA 02215, USA.
  • Juvekar A; Division of Hematology and Oncology, Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS), Boston, MA 02215, USA.
  • Lyssiotis CA; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
  • Lien EC; Department of Pathology, BIDMC, Boston, MA 02215, USA.
  • Albeck JG; Department of Cell Biology, HMS, Boston, MA 02215, USA.
  • Oh D; Department of Molecular and Cellular Biology, FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
  • Varma G; Department of Radiology, BIDMC Boston, MA 02215, USA.
  • Hung YP; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Ullas S; Longwood Small Animal Imaging Facility, BIDMC, Boston, MA 02215, USA.
  • Lauring J; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Seth P; Division of Interdisciplinary Medicine, BIDMC, Boston, MA 02215, USA.
  • Lundquist MR; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
  • Tolan DR; Department of Biology, Boston University, Boston, MA 02215, USA.
  • Grant AK; Department of Radiology, BIDMC Boston, MA 02215, USA.
  • Needleman DJ; Department of Molecular and Cellular Biology, FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
  • Asara JM; Division of Signal Transduction, BIDMC, Boston, MA 02215, USA.
  • Cantley LC; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
  • Wulf GM; 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.
Cell ; 164(3): 433-46, 2016 Jan 28.
Article in En | MEDLINE | ID: mdl-26824656
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phosphatidylinositol 3-Kinases / Fructose-Bisphosphate Aldolase Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phosphatidylinositol 3-Kinases / Fructose-Bisphosphate Aldolase Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: United States