Disruption of XXXX decreases @entity880 export and sensitizes @entity1149 to biguanides independently of the @entity2448 status.

@entity71808 @entity34403 @entity2449 @entity5 @entity2448 @entity19 @entity2 @entity1149 @entity37005 @entity519 @entity880 @entity34742 @entity3338 @entity18706 @entity72157
Most @entity5 rely on aerobic glycolysis to generate energy and metabolic intermediates. To maintain a high glycolytic rate, cells must efficiently export @entity880 through the proton-coupled @entity3338 transporters ( @entity72157 ). These transporters require a chaperone, @entity34403 (BSG) for trafficking to the plasma membrane and function.To validate the key role of these transporters in @entity2 , we first analysed the expression of @entity72157 and BSG in 50 @entity1149 (NSCLC) cases. These proteins were specifically upregulated in @entity5 tissues. We then disrupted BSG in three NSCLC cell lines (A549, H1975 and H292) via 'Zinc-Finger Nucleases'. The three homozygous BSG-/- cell lines displayed a low MCT activity (10- to 5-fold reduction, for @entity34742 and @entity71808 , respectively) compared to wild-type cells. Consequently, the rate of glycolysis, compared to the wild-type counterpart, was reduced by 2.0- to 3.5-fold, whereas the rate of respiration was stimulated in BSG-/- cell lines. Both wild-type and BSG-null cells were extremely sensitive to the mitochondria inhibitor @entity2449 / @entity18706 in normoxia. However, only BSG-null cells, independently of their @entity2448 status, remained sensitive to @entity37005 in @entity519 in vitro and @entity5 growth in @entity19 . Our results demonstrate that inhibiting glycolysis by targeting @entity880 export sensitizes NSCLC to @entity18706 .
