Mouse Genetics Suggests Cell-Context Dependency for Myc-Regulated Metabolic Enzymes during Tumorigenesis

摘要: c-Myc (hereafter called Myc) belongs to a family of transcription factors that regulates cell growth, proliferation, and differentiation. Myc initiates the large cast genes involved in growth by stimulating metabolism protein synthesis. Some these, like those glycolysis, may be part Warburg effect, which is defined as increased glucose uptake lactate production presence adequate oxygen supply. In this study, we have taken mouse-genetics approach challenge role select Myc-regulated metabolic enzymes tumorigenesis vivo. By breeding λ-Myc transgenic mice, Apc(Min) p53 knockout mice with mouse models carrying inactivating alleles Lactate dehydrogenase A (Ldha), 3-Phosphoglycerate (Phgdh) Serine hydroxymethyltransferase 1 (Shmt1), obtained offspring were monitored for tumor development. Very surprisingly, found these are dispensable genetic settings. However, experiments fibroblasts colon carcinoma cells expressing oncogenic Ras show sensitive Ldha knockdown. Our reveal context dependency remarkable ability adapt alterations critical pathways. Thus, achieve clinical success, it will importance correctly stratify patients find synthetic lethal combinations inhibitors targeting enzymes.