Role of ABCC6 in PXE and cancer therapy

ABCC6 is a membrane transporter whose mutations cause the Pseudoxanthoma elasticum (PXE), a complex autosomal recessive disease characterized by ectopic mineralization of soft connective tissues. Although the mechanism of transport of ABCC6 is not completely clear, it is accepted that ABCC6 mediates the efflux of ATP, which is further hydrolyzed in AMP and PPi, a strong inhibitor of mineralization. Previous studies revealed that knockdown of ABCC6 in hepatoma-derived HepG2 caused an alteration in NT5E and TNAP expression1. Both enzymes are involved in the sub sequential metabolism of extracellular ATP and with their activity modulate the balance between inorganic phosphate and pyrophosphate. In a recent study, we have found that silencing of ABCC6 or its pharmacological inhibition with probenecid in HepG2 cells caused a rearrangement of actin filaments in the cytoskeleton and a decrease in migration rate by reducing the efflux of ATP, thus suggesting the hypothesis that ABCC6 could be a target in cancer therapy2. A growing number of evidences are there that flavonoids can modulate the activity of many ABC transporters. We studied the effect of the prototypical flavonoid, quercetin on the cells motility. The preliminary results suggest that ABCC6 activity was modulated by the oxidative stress.