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 language | English |
|---|---|
| Article number | e1336 |
| Journal | Cell Death and Disease |
| Volume | 5 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2014 |
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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 journal › Article
}
TY - JOUR
T1 - Breast cancer stem cells rely on fermentative glycolysis and are sensitive to 2-deoxyglucose treatment
AU - Ciavardelli, D.
AU - Rossi, C.
AU - Barcaroli, D.
AU - Volpe, S.
AU - Consalvo, A.
AU - Zucchelli, M.
AU - De Cola, A.
AU - Scavo, E.
AU - Carollo, R.
AU - D'Agostino, D.
AU - Forlì, F.
AU - D'Aguanno, S.
AU - Todaro, M.
AU - Stassi, G.
AU - Di Ilio, C.
AU - De Laurenzi, V.
AU - Urbani, A.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84905513845&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905513845&partnerID=8YFLogxK
U2 - 10.1038/cddis.2014.285
DO - 10.1038/cddis.2014.285
M3 - Article
C2 - 25032859
AN - SCOPUS:84905513845
VL - 5
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 7
M1 - e1336
ER -