Targeting Unique Metabolic Properties of Breast Tumor Initiating Cells

Overview

Journal Stem Cells

Publisher Oxford University Press

Specialties Cell Biology
Reproductive Medicine

Date 2014 Feb 6

PMID 24497069

Citations 70

Authors

Weiguo Feng

Andrew Gentles

Ramesh V Nair

Min Huang

Yuan Lin

Cleo Y Lee

Shang Cai

Ferenc A Scheeren

Angera H Kuo

Maximilian Diehn

Affiliations

Soon will be listed here.

Abstract

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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