Skip to main content

Advertisement

We’d like to understand how you use our websites in order to improve them. Register your interest.

Phosphoinositide 3-Kinase regulates glycolysis through mobilization of Aldolase A from the actin cytoskeleton

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Gerburg M Wulf.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hu, H., Juvekar, A., Lyssiotis, C. et al. Phosphoinositide 3-Kinase regulates glycolysis through mobilization of Aldolase A from the actin cytoskeleton. Cancer Metab 2, P86 (2014). https://doi.org/10.1186/2049-3002-2-S1-P86

Download citation

Keywords

  • Actin Cytoskeleton
  • Aldolase
  • PI3K Pathway
  • Breast Epithelial Cell
  • Spectrophotometric Assay