期刊
STEM CELLS
卷 32, 期 7, 页码 1734-1745出版社
WILEY
DOI: 10.1002/stem.1662
关键词
Breast tumor initiating cells or cancer stem cells; Metabolic reprogramming; Warburg effect; Dichloroacetic acid; Glycolysis Oxidative phosphorylation
资金
- Sydney Kimmel Foundation
- National Institutes of Health [P30CA147933]
- CRK Faculty Scholar Fund
- Nadia's Gift
- Virginia and D.K. Ludwig Foundation
- Doris Duke Clinical Scientist Development Award
- NIH [1-DP2-CA186569]
Normal stem cells from a variety of tissues display unique metabolic properties compared to their more differentiated progeny. However, relatively little is known about metabolic properties of cancer stem cells, also called tumor initiating cells (TICs). In this study we show that, analogous to some normal stem cells, breast TICs have distinct metabolic properties compared to nontumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs underexpress genes involved in mitochondrial biology and mitochondrial oxidative phosphorylation, and metabolic analyses revealed TICs preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. Mechanistic analyses demonstrated that decreased expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation, plays a critical role in promoting the proglycolytic phenotype of TICs. Metabolic reprogramming via forced activation of Pdh preferentially eliminated TICs both in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and demonstrate that metabolic reprogramming represents a potential therapeutic strategy for targeting these cells.
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