Entry Name Melanoma - Bos taurus (cow)
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 Bos taurus (cow) [GN:
bta ]
Gene 281161 FGF2; fibroblast growth factor 2 precursor [KO:K18497 ]
326284 FGF8; fibroblast growth factor 8 precursor [KO:K04358 ]
326285 FGF10; fibroblast growth factor 10 precursor [KO:K04358 ]
616885 FGF7; fibroblast growth factor 7 precursor [KO:K04358 ]
618474 FGF4; fibroblast growth factor 4 precursor [KO:K04358 ]
533929 FGF18; fibroblast growth factor 18 precursor [KO:K04358 ]
519657 FGF22; fibroblast growth factor 22 precursor [KO:K04358 ]
536771 FGF5; fibroblast growth factor 5 precursor [KO:K04358 ]
281239 IGF1; insulin-like growth factor I preproprotein [KO:K05459 ]
505908 PDGFA; platelet-derived growth factor subunit A precursor [KO:K04359 ]
540106 PDGFB; platelet-derived growth factor subunit B precursor [KO:K17386 ]
613787 PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450 ]
530315 EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357 ]
101905399 LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368 ] [EC:2.7.12.2 ]
282306 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
517948 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
504531 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
282308 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
286865 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
282307 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
615013 BAD; bcl2-associated agonist of cell death [KO:K02158 ]
616369 CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X2 [KO:K06621 ]
513497 CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
617024 E2F2; transcription factor E2F2 isoform X2 [KO:K09389 ]
504939 GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402 ]
618405 GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402 ]
505463 GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402 ]
407219 MITF; microphthalmia-associated transcription factor isoform M- [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
