Induction of melanogenesis during the various melanoma growth phases and the role of tyrosinase, lysosome-associated membrane proteins, and p90 calnexin in the melanogenesis cascade

Melanin biosynthesis (melanogenesis) is a metabolic pathway exclusively expressed by melanocytes and melanoma cells, and is often altered and/or markedly elevated in the latter cells. The changes in melanogenesis may be responsible for some of the clinical and histopathological features unique to melanoma. Melanogenesis may also contribute to the malignant transformation of melanoma precursors (i.e., atypical moles [or dysplastic nevi]) to melanoma as seen in patients with the familial atypical multiple-mole-melanoma (FAMMM) syndrome. However, it does not appear to affect the multi-step growth phases of melanoma cells from radial to vertical and lastly metastatic growth phases. Within the melanosomal compartment, eu- and pheomelanin pigments are synthesized. Both tyrosinase and lysosome-associated membrane protein (LAMP) gene products play important roles in this process. A coordinated interaction between these two gene family products is required for melanogenesis to occur properly. p90 calnexin is a new melanosome-associated molecule that is presumed to function as a melanogenesis chaperone by controlling the assembly and folding of glycoprotein intermediates of tyrosinase and LAMP gene families.