Myosin-Va Contributes to Manifestation of Malignant-Related Properties in Melanoma Cells

Melanoma is a highly metastatic and therapeutically resistant cancer, whose incidence has more than tripled in the last decades (Smalley et al., 2010). Physiologically, melanocytes produce and store melanin pigments in the melanosomes, which are transported to the cell periphery and transferred to keratinocytes, a process that requires the tripartite complex Rab27a/melanophilin/myosin-Va (Hume and Seabra, 2011). Myosin-Va is an actin-based molecular motor that also serves a multitude of other functions, such as plasma membrane receptor recycling, exocytosis, association with nuclear speckles and the centrosome (see Woolner and Bement, 2010); interaction with PTEN, thereby modulating PI3K pathway (van Diepen et al., 2009), interaction with Bcl-xL, proposed to promote invasion of islettumor cells (Du et al., 2007); as biomarker of invasiveness for nonfunctioning pituitary adenomas (Galland et al., 2010). Moreover, myosin-Va was shown to be up-regulated by Snail to promote cancer cell invasion (Lan et al., 2010), and was postulated to control apoptosis by sequestering the pro-apoptotic protein Bmf, which is unleashed upon loss of cell attachment (Puthalakath et al., 2001).