The Glucose Dependent Transcription Factor ChREBP Contributes to Glucose-Dependent Anabolic Synthesis and Cell Proliferation

Xuemei Tong¹, Anthony Mancuso², Fangping Zhao, Joshua J. Gruber, Craig B. Thompson

Many human tumors display high rates of aerobic glycolysis, de novo fatty acid synthesis and nucleotide biosynthesis. Although these metabolic alterations might not be initiating events in oncogenesis, blocking them may be a useful strategy for slowing carcinogenesis. The carbohydrate responsive element binding protein (ChREBP) is a critical mediator of glucose-dependent metabolism. In this study, the metabolic effects of ChREBP knockdown in human colon cancer cells were examined with ¹³C NMR and ¹⁴C scintillation. The results demonstrated that knockdown reduced aerobic glycolysis and growth-related biosynthesis. It also increased TCA cycle flux and oxygen consumption, resulting in a less cancerous phenotype.