The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces nutrient flexibility.

ABSTRACT: As noted by Warburg, many cancer cells depend on the consumption of glucose. We performed a genetic screen to identify factors responsible for glucose addiction and recovered the two subunits of the xCT antiporter (system x_c^-), which plays an antioxidant role by exporting glutamate for cystine. Disruption of the xCT antiporter greatly improves cell viability after glucose withdrawal, because conservation of glutamate enables cells to maintain mitochondrial respiration. In some breast cancer cells, xCT antiporter expression is upregulated through the antioxidant transcription factor Nrf2 and contributes to their requirement for glucose as a carbon source. In cells carrying patient-derived mitochondrial DNA mutations, the xCT antiporter is upregulated and its inhibition

SUBMITTER: Shin CS 

PROVIDER: S-EPMC5413954 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature