TY - JOUR
T1 - Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton
AU - Hu, Hai
AU - Juvekar, Ashish
AU - Lyssiotis, Costas A.
AU - Lien, Evan C.
AU - Albeck, John G.
AU - Oh, Doogie
AU - Varma, Gopal
AU - Hung, Yin Pun
AU - Ullas, Soumya
AU - Lauring, Josh
AU - Seth, Pankaj
AU - Lundquist, Mark R.
AU - Tolan, Dean R.
AU - Grant, Aaron K.
AU - Needleman, Daniel J.
AU - Asara, John M.
AU - Cantley, Lewis C.
AU - Wulf, Gerburg M.
N1 - Funding Information:
L.C.C. and G.M.W. are supported by a Stand Up to Cancer Dream Team Translational Research Grant, (SU2C-AACR-DT0209), by the Breast Cancer Research Foundation (BCRF), the Mary Kay Ash Foundation, the Men’s Initiative of DFHCC, and the Breast Cancer Alliance; L.C.C. by NIH grant GM041890; J.M.A. in part by NIH NCI grants 5P01CA120964-05 and 5P30CA006516-46; A.K.G., P.S., and G.V. in part by NIH R21 EB014471 and R01 CA169470; and P.S. in part by R01CA152330-0. D.J.N. is supported in part by NSF DBI-0959721 and DMR-0820484 and the United States – Israel Binational Science Foundation (BSF 2009271); and C.A.L. by a Dale F. Frey award from the Damon Runyon Cancer Research Foundation.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/1/28
Y1 - 2016/1/28
N2 - Summary 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.
AB - Summary 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.
UR - http://www.scopus.com/inward/record.url?scp=84955560430&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955560430&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2015.12.042
DO - 10.1016/j.cell.2015.12.042
M3 - Article
C2 - 26824656
AN - SCOPUS:84955560430
SN - 0092-8674
VL - 164
SP - 433
EP - 446
JO - Cell
JF - Cell
IS - 3
ER -