LAUSR

Previous studies have shown that Peroxisome Proliferator-Activated Receptor Gamma, Coactivator 1β (PGC-1β) and Estrogen-Related Receptor alpha (ERRα) are over-expressed in colorectal cancer to promote tumor survival. In this study, we show that amino acid motif LRELL on PGC-1β is responsible for the physical interaction with ERRα and promotes ERRα mRNA and protein expression. Using RNAsequencing, we found that mitochondrial Phosphoenolpyruvate Carboxykinase 2 (PCK2) decreased the most after depletion of both PGC-1β and ERRα. Depletion of PCK2 was sufficient to reduce anchorage-independent growth and inhibit glutamine utilization by the TCA cycle. Lastly, shRNA mediated depletion of ERRα decreased anchorage independent growth and glutamine metabolism, which could not be rescued by plasmid derived expression of PCK2. These findings suggest that transcriptional control of PCK2 is one mechanism used PGC-1β and ERRα to promote glutamine metabolism and colorectal cancer cell survival.