Abstract
Cutaneous malignant melanoma is one of the most serious skin cancers and is highly invasive and markedly resistant to conventional therapy. Melanomagenesis is initially triggered by environmental agents including ultraviolet (UV), which induces genetic/epigenetic alterations in the chromosomes of melanocytes. In human melanomas, the RAS/RAF/MEK/ERK (MAPK) and the PI3K/PTEN/AKT (AKT) signaling pathways are two major signaling pathways and are constitutively activated through genetic alterations. Mutations of RAF, RAS, and PTEN contribute to antiapoptosis, abnormal proliferation, angiogenesis, and invasion for melanoma development and progression. To find better approaches to therapies for patients, understanding these MAPK and AKT signaling mechanisms of melanoma development and progression is important. Here, we review MAPK and AKT signaling networks associated with melanoma development and progression.
Highlights
Melanoma progression is closely associated with oncogenic change: (1) genetic alteration and (2) epigenetic alteration
This pathway is constitutively activated by growth factors such as stem cell factor (SCF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and glial-cell-derived neurotrophic factor (GDNF) [37, 38], though activation of this signal is weak in melanocytes
NRAS and BRAF genes are mutated in 15% to 30% and in 50% to 70% of human melanomas, respectively, leading to their permanent activation [41] followed by promotion of proliferation, survival, invasion, and angiogenesis of melanoma [42, 43]
Summary
Melanoma progression is closely associated with oncogenic change: (1) genetic alteration (heritable changes in the DNA sequence such as gene mutations, deletions, amplifications, or translocations) and (2) epigenetic alteration. Much information associated with melanoma development such as information on gene mutations, alterations of gene expression patterns, and protein activities has been reported. The RAS/RAF/MEK/ERK pathway, one of the most well-known pathways involved in melanoma progression, is regulated by receptor tyrosine kinases, cytokines, and heterotrimeric G-protein-coupled receptors [35].
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