Unknown,Transcriptomics,Genomics,Proteomics

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Targeting Unique Metabolic Properties of Breast Tumor Initiating Cells


ABSTRACT: Bulk cancer cell populations are known to display distinct metabolic properties compared to their normal counterparts. However, relatively little is known about heterogeneity of metabolic properties within tumors. In this study we show that, analogous to some normal stem cells, breast tumor initiating cells (TICs, also called cancer stem cells) have distinct metabolic properties compared to non-tumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs under-express genes involved in mitochondrial oxidative phosphorylation and although TICs are relatively quiescent, they preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. TICs contain fewer mitochondria and display lower expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation. Metabolic reprogramming of TICs by pharmacologic activation of Pdh preferentially eliminates TICs in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and indicate that metabolic reprogramming represents a promising strategy for targeting these cells. Examination transcriptome profiles for breast tumor initiating cells (TICs) and non-tumorigenic cells (NTCs)

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Gentles 

PROVIDER: E-GEOD-41286 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Targeting unique metabolic properties of breast tumor initiating cells.

Feng Weiguo W   Gentles Andrew A   Nair Ramesh V RV   Huang Min M   Lin Yuan Y   Lee Cleo Y CY   Cai Shang S   Scheeren Ferenc A FA   Kuo Angera H AH   Diehn Maximilian M  

Stem cells (Dayton, Ohio) 20140701 7


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 mi  ...[more]

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