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

D. Ciavardelli, C. Rossi, D. Barcaroli, S. Volpe, A. Consalvo, M. Zucchelli, A. De Cola, E. Scavo, R. Carollo, D. D'Agostino, F. Forlì, S. D'Aguanno, M. Todaro, G. Stassi, C. Di Ilio, V. De Laurenzi, A. Urbani

Research output: Contribution to journalArticle

107 Citations (Scopus)

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.

Original languageEnglish
Article numbere1336
JournalCell Death and Disease
Volume5
Issue number7
DOIs
Publication statusPublished - 2014

Fingerprint

Neoplastic Stem Cells
Deoxyglucose
Glycolysis
Breast Neoplasms
Proteomics
Neoplasms
Therapeutics
Glucose
Recurrence
Pyruvate Kinase
Metabolomics
Oxidative Phosphorylation
Growth
L-Lactate Dehydrogenase
Doxorubicin
Oxidation-Reduction
Oxidoreductases
Protein Isoforms
Cell Proliferation
Radiation

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Breast cancer stem cells rely on fermentative glycolysis and are sensitive to 2-deoxyglucose treatment. / Ciavardelli, D.; Rossi, C.; Barcaroli, D.; Volpe, S.; Consalvo, A.; Zucchelli, M.; De Cola, A.; Scavo, E.; Carollo, R.; D'Agostino, D.; Forlì, F.; D'Aguanno, S.; Todaro, M.; Stassi, G.; Di Ilio, C.; De Laurenzi, V.; Urbani, A.

In: Cell Death and Disease, Vol. 5, No. 7, e1336, 2014.

Research output: Contribution to journalArticle

Ciavardelli, D, Rossi, C, Barcaroli, D, Volpe, S, Consalvo, A, Zucchelli, M, De Cola, A, Scavo, E, Carollo, R, D'Agostino, D, Forlì, F, D'Aguanno, S, Todaro, M, Stassi, G, Di Ilio, C, De Laurenzi, V & Urbani, A 2014, 'Breast cancer stem cells rely on fermentative glycolysis and are sensitive to 2-deoxyglucose treatment', Cell Death and Disease, vol. 5, no. 7, e1336. https://doi.org/10.1038/cddis.2014.285
Ciavardelli, D. ; Rossi, C. ; Barcaroli, D. ; Volpe, S. ; Consalvo, A. ; Zucchelli, M. ; De Cola, A. ; Scavo, E. ; Carollo, R. ; D'Agostino, D. ; Forlì, F. ; D'Aguanno, S. ; Todaro, M. ; Stassi, G. ; Di Ilio, C. ; De Laurenzi, V. ; Urbani, A. / Breast cancer stem cells rely on fermentative glycolysis and are sensitive to 2-deoxyglucose treatment. In: Cell Death and Disease. 2014 ; Vol. 5, No. 7.
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AU - Rossi, C.

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AU - Consalvo, A.

AU - Zucchelli, M.

AU - De Cola, A.

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AU - De Laurenzi, V.

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