Na+/Ca2+ Exchanger (NCX) and Ca2+ homeostasis in human melanoma model cells with the B-RAFV600E and NRASQ61R mutations
Calcium is a ubiquitous intracellular second messenger, playing central roles in the regulation of several biological processes. Alterations in Ca2+ homeostasis and signaling are an important feature of tumor cells to acquire proliferative and survival advantages, which include structural and functional changes in storage capacity, channels, and pumps. Here,we investigated the differences in Ca2+ homeostasis in vemurafenib-responsive and nonresponsive melanoma cells. Also, the expression of the Na+/Ca2+ exchanger (NCX) and the impact of its inhibition were studied. For this, it was used BRAFV600E (SK-MEL-19) and NRASQ6IR (SK-MEL-147) mutated human melanoma cells. The intracellular Ca2+chelator BAPTA-AM decreased the viability of SK-MEL-147 but not of SK-MEL-19 and EGTA sensitized NRASQ6IR -mutated cells to vemurafenib. These cells also presented a smaller response to thapsargin and ionomycin regarding the cytosolic Ca2+ levels in relation to SK-MEL-19, which was associated to an increased expression of NCX1, NO basal levels, and sensitivity to NCX
inhibitors. These data highlight the differences between BRAFV600E and NRASQ6IR - mutated melanoma cells in response to Ca2+ stimuli and point to the potential combination of clinically used chemotherapeutic drugs, including vemurafenib, with NCX inhibitors as a new therapeutic strategy to the treatment of melanoma.