Entry Name Melanoma - Macaca mulatta (rhesus monkey)
Description Melanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes. The only known environmental risk factor is exposure to ultraviolet (UV) light and in people with fair skin the risk is greatly increased. Melanoma pathogenesis is also driven by genetic factors. Oncogenic NRAS mutations activate both effector pathways Raf-MEK-ERK and PI3K-Akt. The Raf-MEK-ERK pathway may also be activated via mutations in the BRAF gene. The PI3K-Akt pathway may be activated through loss or mutation of the inhibitory tumor suppressor gene PTEN. These mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Melanoma development has been shown to be strongly associated with inactivation of the p16INK4a/cyclin dependent kinases 4 and 6/retinoblastoma protein (p16INK4a/CDK4,6/pRb) and p14ARF/human double minute 2/p53 (p14ARF/HMD2/p53) tumor suppressor pathways. MITF and TP53 are implicated in further melanoma progression.
Class Human Diseases; Cancer: specific typesBRITE hierarchy
Pathway map Ortholog table Organism Macaca mulatta (rhesus monkey) [GN:
mcc ]
Gene 574345 FGF7; fibroblast growth factor 7 precursor [KO:K04358 ]
701584 FGF10; fibroblast growth factor 10 precursor [KO:K04358 ]
702727 FGF22; fibroblast growth factor 22 precursor [KO:K04358 ]
708918 FGF3; fibroblast growth factor 3 precursor [KO:K04358 ]
706659 FGF17; fibroblast growth factor 17 precursor [KO:K04358 ]
695896 FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358 ]
710643 FGF23; fibroblast growth factor 23 precursor [KO:K22428 ]
698444 IGF1; insulin-like growth factor I precursor [KO:K05459 ]
707725 PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359 ]
703173 PDGFB; platelet-derived growth factor subunit B [KO:K17386 ]
704310 PDGFD; platelet-derived growth factor D isoform X2 [KO:K05450 ]
698619 EGF; pro-epidermal growth factor isoform X2 [KO:K04357 ]
721821 MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369 ] [EC:2.7.12.2 ]
716098 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
709959 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
710552 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
707310 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
719367 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
698996 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
717740 BAD; bcl2-associated agonist of cell death [KO:K02158 ]
719199 CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
713904 E2F3; transcription factor E2F3 isoform X1 [KO:K06620 ]
697835 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
701054 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
711257 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
114672263 LOW QUALITY PROTEIN: DNA damage-binding protein 2-like [KO:K10140 ]
695537 MITF; microphthalmia-associated transcription factor [KO:K09455 ]
Compound C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Miller AJ, Mihm MC Jr.
Title Melanoma.
Journal Reference Authors Chin L.
Title The genetics of malignant melanoma: lessons from mouse and man.
Journal Reference Authors Takata M, Saida T.
Title Genetic alterations in melanocytic tumors.
Journal Reference Authors Chudnovsky Y, Khavari PA, Adams AE.
Title Melanoma genetics and the development of rational therapeutics.
Journal Reference Authors Merlino G.
Title Cancer biology: the weakest link?
Journal Reference Authors Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR.
Title Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.
Journal Reference Authors Levy C, Khaled M, Fisher DE.
Title MITF: master regulator of melanocyte development and melanoma oncogene.
Journal Reference Authors Tsao H, Goel V, Wu H, Yang G, Haluska FG.
Title Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma.
Journal Reference Authors Gruss C, Herlyn M.
Title Role of cadherins and matrixins in melanoma.
Journal Reference Authors Thompson JF, Scolyer RA, Kefford RF.
Title Cutaneous melanoma.
Journal Reference Authors Omholt K, Platz A, Kanter L, Ringborg U, Hansson J.
Title NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression.
Journal Clin Cancer Res 9:6483-8 (2003)
Reference Authors Hussein MR.
Title The TP53 tumor suppressor gene and melanoma tumorigenesis: is there a relationship?
Journal Reference Authors Lazar-Molnar E, Hegyesi H, Toth S, Falus A.
Title Autocrine and paracrine regulation by cytokines and growth factors in melanoma.
Journal Related KO pathway LinkDB All DBs
