Additionally, the apoptosis repressor with caspase recruitment domain (ARC) proteins appears essential in preventing Caspase-8 activation in melanoma cells under ER stress.481 Inhibiting the MEK/ERK pathway makes melanoma cells more susceptible to apoptosis induced by ER stress, partially through caspase-4 activation, and is also associated with the inhibition of ER chaperon glucose-regulated protein 78 (GRP78) production.482. This evidence concerns the gene HSPA5 and melanoma.