RSK Regulates PFK-2 Activity to Promote Metabolic Rewiring in Melanoma.

摘要: Metabolic reprogramming is a hallmark of cancer that includes increased glucose uptake and accelerated aerobic glycolysis. This phenotype required to fulfill anabolic demands associated with aberrant cell proliferation often mediated by oncogenic drivers such as activated BRAF. In this study, we show the MAPK-activated p90 ribosomal S6 kinase (RSK) necessary maintain glycolytic metabolism in BRAF-mutated melanoma cells. RSK directly phosphorylated regulatory domain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), an enzyme catalyzes synthesis fructose-2,6-bisphosphate during Inhibition reduced PFKFB2 activity flux cells, suggesting important role for BRAF-mediated metabolic rewiring. Consistent this, expression phosphorylation-deficient mutant decreased glycolysis growth mice. Together, these results indicate RSK-mediated phosphorylation plays key melanomas.Significance: promotes driving enzyme. Cancer Res; 78(9); 2191-204. ©2018 AACR.