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Cell Death Dis. 2014 Jul 17;5:e1336. doi: 10.1038/cddis.2014.285.

Breast cancer stem cells rely on fermentative glycolysis and are sensitive to 2-deoxyglucose treatment.

Author information

1
1] School of Human and Social Science, 'Kore' University of Enna, Enna, Italy [2] Center of Excellence on Aging (Ce.S.I.), 'G. d'Annunzio' Foundation, Chieti, Italy.
2
1] Center of Excellence on Aging (Ce.S.I.), 'G. d'Annunzio' Foundation, Chieti, Italy [2] Department of Experimental and Clinical Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy.
3
Department of Surgical and Oncological Sciences, Laboratory of Cellular and Molecular Pathophysiology, University of Palermo, Palermo, Italy.
4
IRCCS S. Lucia, Rome, Italy.
5
Department of Experimental and Clinical Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy.
6
1] IRCCS S. Lucia, Rome, Italy [2] Department of Internal Medicine, University of Rome 'Tor Vergata', Rome, Italy.

Abstract

A number of studies suggest that cancer stem cells are essential for tumour growth, and failure to target these cells can result in tumour relapse. As this population of cells has been shown to be resistant to radiation and chemotherapy, it is essential to understand their biology and identify new therapeutic approaches. Targeting cancer metabolism is a potential alternative strategy to counteract tumour growth and recurrence. Here we applied a proteomic and targeted metabolomic analysis in order to point out the main metabolic differences between breast cancer cells grown as spheres and thus enriched in cancer stem cells were compared with the same cells grown in adherent differentiating conditions. This integrated approach allowed us to identify a metabolic phenotype associated with the stem-like condition and shows that breast cancer stem cells (BCSCs) shift from mitochondrial oxidative phosphorylation towards fermentative glycolysis. Functional validation of proteomic and metabolic data provide evidences for increased activities of key enzymes of anaerobic glucose fate such as pyruvate kinase M2 isoform, lactate dehydrogenase and glucose 6-phopshate dehydrogenase in cancer stem cells as well as different redox status. Moreover, we show that treatment with 2-deoxyglucose, a well known inhibitor of glycolysis, inhibits BCSC proliferation when used alone and shows a synergic effect when used in combination with doxorubicin. In conclusion, we suggest that inhibition of glycolysis may be a potentially effective strategy to target BCSCs.

PMID:
25032859
PMCID:
PMC4123079
DOI:
10.1038/cddis.2014.285
[Indexed for MEDLINE]
Free PMC Article

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