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Breast Cancer Research
Published in: Breast Cancer Research 5/2014

Open Access 01-10-2014 | Research article

Mitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential

Authors: Hélène Pelicano, Wan Zhang, Jinyun Liu, Naima Hammoudi, Jiale Dai, Rui-Hua Xu, Lajos Pusztai, Peng Huang

Published in: Breast Cancer Research | Issue 5/2014

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Abstract

Introduction

Triple-negative breast cancer (TNBC) is a subtype of highly malignant breast cancer with poor prognosis. TNBC is not amenable to endocrine therapy and often exhibit resistance to current chemotherapeutic agents, therefore, further understanding of the biological properties of these cancer cells and development of effective therapeutic approaches are urgently needed.

Methods

We first investigated the metabolic alterations in TNBC cells in comparison with other subtypes of breast cancer cells using molecular and metabolic analyses. We further demonstrated that targeting these alterations using specific inhibitors and siRNA approach could render TNBC cells more sensitive to cell death compared to other breast cancer subtypes.

Results

We found that TNBC cells compared to estrogen receptor (ER) positive cells possess special metabolic characteristics manifested by high glucose uptake, increased lactate production, and low mitochondrial respiration which is correlated with attenuation of mTOR pathway and decreased expression of p70S6K. Re-expression of p70S6K in TNBC cells reverses their glycolytic phenotype to an active oxidative phosphorylation (OXPHOS) state, while knockdown of p70S6K in ER positive cells leads to suppression of mitochondrial OXPHOS. Furthermore, lower OXPHOS activity in TNBC cells renders them highly dependent on glycolysis and the inhibition of glycolysis is highly effective in targeting TNBC cells despite their resistance to other anticancer agents.

Conclusions

Our study shows that TNBC cells have profound metabolic alterations characterized by decreased mitochondrial respiration and increased glycolysis. Due to their impaired mitochondrial function, TNBC cells are highly sensitive to glycolytic inhibition, suggesting that such metabolic intervention may be an effective therapeutic strategy for this subtype of breast cancer cells.
Appendix
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Metadata
Title
Mitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential
Authors
Hélène Pelicano
Wan Zhang
Jinyun Liu
Naima Hammoudi
Jiale Dai
Rui-Hua Xu
Lajos Pusztai
Peng Huang
Publication date
01-10-2014
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2014
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-014-0434-6

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