Volume 2 Supplement 1
Phosphoinositide 3-Kinase regulates glycolysis through mobilization of Aldolase A from the actin cytoskeleton
© Hu et al; licensee BioMed Central Ltd. 2014
Published: 28 May 2014
Phosphoinositide 3-Kinase (PI3K) has been shown to modulate multiple steps in glucose uptake and metabolism through activation of the protein kinase, AKT. In order to dissect the contributions of PI3K-pathway components, we examined the effects of specific enzyme inhibitors on the regulation of glycolysis.
We measured reduction of NAD to NADH, occurring at the GAPDH step, as a read-out for glycolysis in living cells; mass spectroscopy to determine the relative abundance of glycolytic metabolites in breast cell cultures and in a mouse model of breast cancer; immunoblotting and confocal live cell microscopy to delineate the intracellular signaling cascade downstream from PI3K and a spectrophotometric assay to determine Aldolase activity.
In breast epithelial cells PI3K-, but not AKT-, SGK- or mTOR-inhibitors cause a significant decrease in glycolysis at the step catalyzed by Aldolase A. We show that growth factors stimulate Aldolase A release from the actin cytoskeleton and an increase in cellular Aldolase activity in a PI3K dependent manner. The mobilization and activation of Aldolase is dependent on Rac1-catalyzed phosphorylation of p-21 activated kinase (PAK) and subsequent mobilization of the actin cytoskeleton.
This newly identified AKT- and mTOR-independent role of PI3K in controlling glucose metabolism has important implications in regard to utilization of PI3K pathway inhibitors for treatment of epithelial cancers.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.