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

被引：304

作者：

Hu, Hai ^{[1
,2
]}

Juvekar, Ashish ^{[1
,2
]}

Lyssiotis, Costas A. ^{[3
,14
]}

Lien, Evan C. ^{[4
]}

Albeck, John G. ^{[5
,15
]}

Oh, Doogie ^{[6
]}

Varma, Gopal ^{[7
]}

Hung, Yin Pun ^{[8
]}

Ullas, Soumya ^{[13
]}

Lauring, Josh ^{[9
]}

Seth, Pankaj ^{[10
]}

Lundquist, Mark R. ^{[3
]}

Tolan, Dean R. ^{[11
]}

Grant, Aaron K. ^{[7
]}

Needleman, Daniel J. ^{[6
]}

Asara, John M. ^{[12
]}

Cantley, Lewis C. ^{[3
]}

Wulf, Gerburg M. ^{[1
,2
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA

[2] Harvard Univ, Med Sch HMS, Boston, MA 02215 USA

[3] Weill Cornell Med, Meyer Canc Ctr, New York, NY 10065 USA

[4] BIDMC, Dept Pathol, Boston, MA 02215 USA

[5] HMS, Dept Cell Biol, Boston, MA 02215 USA

[6] Harvard Univ, FAS Ctr Syst Biol, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[7] BIDMC Boston, Dept Radiol, Boston, MA 02215 USA

[8] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[9] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA

[10] BIDMC, Div Interdisciplinary Med, Boston, MA 02215 USA

[11] Boston Univ, Dept Biol, Boston, MA 02215 USA

[12] BIDMC, Div Signal Transduct, Boston, MA 02215 USA

[13] BIDMC, Longwood Small Anim Imaging Facil, Boston, MA 02215 USA

[14] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA

[15] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA

来源：

CELL | 2016年 / 164卷 / 03期

关键词：

BREAST-CANCER; F-ACTIN; INHIBITOR; METABOLISM; ACTIVATION; PATHWAY; KINASE; CELLS; RAC; DEHYDROGENASE;

D O I：

10.1016/j.cell.2015.12.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：433 / 446

页数：14

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