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

Andrea Urbani, 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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

149 Citazioni (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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
Numero di pagine12
RivistaCELL DEATH & DISEASE
Volume5
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • PYRUVATE-KINASE M2
  • TUMOR-GROWTH

Fingerprint

Entra nei temi di ricerca di 'Breast cancer stem cells rely on fermentative glycolysis and are sensitive to 2-deoxyglucose treatment'. Insieme formano una fingerprint unica.

Cita questo