Inhibition of retinoic acid receptor β signaling confers glycolytic dependence and sensitization to dichloroacetate in melanoma cells.

ABSTRACT: Dysregulation of metabolism during melanoma progression is tightly associated with the acquisition of genetic and epigenetic alterations in regulators of metabolic pathways. Retinoic acid receptor beta (RARβ) is epigenetically silenced in a large proportion of melanomas, but a link between RARβ and metabolic rewiring of melanoma has not been established. Here, we show that in primary human melanocytes, all-trans retinoic acid (a RARβ agonist) induced growth inhibition accompanied by a decrease in both glycolytic and oxidative metabolism, whereas selective inhibition of RARβ led to an increase in the basal glycolytic rate and increased sensitivity to inhibition of glycolysis. In melanoma cells, inhibition of RARβ promoted lower mitochondrial respiration and higher glycolytic activity, which

SUBMITTER: Abildgaard C 

PROVIDER: S-EPMC5663589 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature