Project description: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)
Project description: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.
Project description:We investigated the changes in acetylation peaks on H3K27ac in cells in response to inhibitors that alter the activity of acetyl-coa generating enzymes
Project description:We investigated gene expression changes in response to acetate treatment, which results in increased MIC-frequency, H3K27ac, and metastatic potential.