Metabolic reprogramming – shifting from oxidative phosphorylation to aerobic glycolysis and glutaminolysis – provides a mechanism for cancer cells to meet the energy demands required to maintain increased proliferation and survival. Many cancer mutations serve to support this reprogramming, which is also promoted by the c-Myc oncogene signaling pathway. In a recent FASEB Journal publication, researchers led by Dr. Ande Satyanarayana have identified Id1 (Inhibitor of Differentiation 1) as another oncogene that promotes metabolic reprogramming – and that it does so through a positive feedback mechanism with c-Myc.
Together with other GRU colleagues, Drs. Satyanarayana, Bal Krishan Sharma, Ravindra Kolhe, and Nahid Mivechi showed that Id1 and c-Myc work downstream of MAPK/ERK signaling and in concert with each other to reprogram the metabolic processes of HCCs. They demonstrate that aerobic glycolysis supported by c-Myc and Id1 is thwarted by knockdown of either Id1 or c-Myc. They further determined that in anaerobic conditions, Hif1-alpha down-regulates both Id1 and c-Myc through Mxi1. Results identify Id1 as a potential marker for HCC and support its role in the metabolic reprogramming of HCCs.[Sharma BK, Kolhe R, Black SM, Keller JR, Mivechi NF, Satyanarayana A. Inhibitor of differentiation 1 transcription factor promotes metabolic reprogramming in hepatocellular carcinoma cells. FASEB J. 2015 Sep 1. pii: fj.15-277749. [Epub ahead of print]]