ER stress-induced autophagy in melanoma

The activation of RAF-MEK-extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade by v-raf murine sarcoma viral oncogene homolog B1 (BRAF)(V600E) mutation is a key alteration in melanoma. Although BRAF inhibitor (BRAFi) has achieved remarkable clinical success, the positive response to BRAFi is not sustainable, and the initial clinical benefit is eventually barred by the development of resistance to BRAFi. There is growing evidence to suggest that endoplasmic reticulum (ER) stress-induced autophagy could be a potential pro-survival mechanism that contributes to genesis of melanoma and to the resistance to BRAFi. ER stress-induced autophagy is an evolutionarily conserved membrane process. By degrading and recycling proteins and organelles via the formation of autophagous vesicles and their fusion with lysosomes, the autophagy plays a key role in homeostasis as well as pathological processes. In this review, we examine the autophagy phenomenon in melanocytic nevus, primary and metastatic melanoma, and its significance in BRAFi-resistant melanoma.