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Cell. 2016 Jan 28;164(3):433-46. doi: 10.1016/j.cell.2015.12.042.

Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton.

Author information

1
Division of Hematology and Oncology, Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS), Boston, MA 02215, USA.
2
Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
3
Department of Pathology, BIDMC, Boston, MA 02215, USA.
4
Department of Cell Biology, HMS, Boston, MA 02215, USA.
5
Department of Molecular and Cellular Biology, FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
6
Department of Radiology, BIDMC Boston, MA 02215, USA.
7
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
8
Longwood Small Animal Imaging Facility, BIDMC, Boston, MA 02215, USA.
9
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
10
Division of Interdisciplinary Medicine, BIDMC, Boston, MA 02215, USA.
11
Department of Biology, Boston University, Boston, MA 02215, USA.
12
Division of Signal Transduction, BIDMC, Boston, MA 02215, USA.
13
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.

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.

PMID:
26824656
PMCID:
PMC4898774
DOI:
10.1016/j.cell.2015.12.042
[Indexed for MEDLINE]
Free PMC Article

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