Differential crosstalk between the AMPK and PI3K/Akt pathways in breast cancer cells of differing genotypes: Leptin inhibits the effectiveness of AMPK activation

El-Masry,Omar S.; Al-Sakkaf,Kaltoom; Brown,Barry L.; Dobson,Pauline R.M.

doi:10.3892/or.2015.4198

Differential crosstalk between the AMPK and PI3K/Akt pathways in breast cancer cells of differing genotypes: Leptin inhibits the effectiveness of AMPK activation

Authors:
- Omar S. El-Masry
- Kaltoom Al-Sakkaf
- Barry L. Brown
- Pauline R.M. Dobson
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Affiliations: Department of Human Metabolism, The Medical School, University of Sheffield, Sheffield, S10 2RX, UK
Published online on: August 11, 2015 https://doi.org/10.3892/or.2015.4198
Pages: 1675-1680
Copyright: © El-Masry et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

AMP-activated protein kinase (AMPK), a sensor of cellular energy, is widely reported as a potential therapeutic target in treatment of breast and other cancers. The activated enzyme has been shown to be a promising anti-proliferative agent in breast cancer cell lines. However, little data exist on crosstalk between AMPK and the cellular survival axis of PI3K/Akt/mTOR pathway and the impact of microenvironment on cellular responses to AMPK activation. We present results which show differential crosstalk between AMPK and Akt, dependent on the cellular genetics of each breast cancer cell type. We also show that leptin blocks activation of AMPK and partially or completely attenuates the anti-proliferative effect of AMPK activation depending on the cell type. This suggests that leptin within the local environment might impose limitations on therapeutic usage of AMPK activators in cancer, thereby attenuating their effective use in many obese subjects.

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