KEGG   PATHWAY: pteh05218
Entry
pteh05218                   Pathway                                
Name
Melanoma - Piliocolobus tephrosceles (Ugandan red Colobus)
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 types
Pathway map
pteh05218  Melanoma
pteh05218

Organism
Piliocolobus tephrosceles (Ugandan red Colobus) [GN:pteh]
Gene
111523283  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
111546245  FGF2; fibroblast growth factor 2 [KO:K18497]
111528737  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
111534218  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
111552814  FGF7; fibroblast growth factor 7 [KO:K04358]
111522276  FGF3; fibroblast growth factor 3 [KO:K04358]
111522486  FGF4; fibroblast growth factor 4 [KO:K04358]
111535838  FGF6; fibroblast growth factor 6 [KO:K04358]
111536051  FGF16; fibroblast growth factor 16 [KO:K04358]
111525307  FGF9; fibroblast growth factor 9 [KO:K04358]
111547150  FGF18; fibroblast growth factor 18 [KO:K04358]
111547417  FGF20; fibroblast growth factor 20 [KO:K04358]
111538699  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
111549401  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
111522468  FGF19; fibroblast growth factor 19 [KO:K22603]
111519986  FGF21; fibroblast growth factor 21 [KO:K22429]
111535828  FGF23; fibroblast growth factor 23 [KO:K22428]
111552446  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
111523785  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
111523727  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
111549133  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
111553384  PDGFC; platelet-derived growth factor C [KO:K05450]
111540080  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
111547933  EGF; pro-epidermal growth factor [KO:K04357]
111544121  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
111553422  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
111548389  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
111520430  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
111552670  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
111555709  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111540622  KRAS; GTPase KRas isoform X1 [KO:K07827]
111549619  NRAS; GTPase NRas [KO:K07828]
111536410  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
111521522  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
111546904  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111548354  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111521954  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111530673  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111525729  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
111522272  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
111541790  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
111521403  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111544647  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111523340  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111554247  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111539891  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111548774  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
111554120  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111545216  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111538340  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111522294  BAD; bcl2-associated agonist of cell death [KO:K02158]
111551321  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
111528609  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
111527100  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
111542983  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
111552475  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
111523077  RB1; retinoblastoma-associated protein [KO:K06618]
111548151  E2F1; transcription factor E2F1 [KO:K17454]
111547703  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
111541114  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
111541390  CDH1; cadherin-1 isoform X1 [KO:K05689]
111541101  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
111528537  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
111520681  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
111520083  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
111542928  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
111544893  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
111539938  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
111533368  MITF; microphthalmia-associated transcription factor isoform X2 [KO:K09455]
Compound
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166
Reference
  Authors
Chin L.
  Title
The genetics of malignant melanoma: lessons from mouse and man.
  Journal
Nat Rev Cancer 3:559-70 (2003)
DOI:10.1038/nrc1145
Reference
  Authors
Takata M, Saida T.
  Title
Genetic alterations in melanocytic tumors.
  Journal
J Dermatol Sci 43:1-10 (2006)
DOI:10.1016/j.jdermsci.2006.05.002
Reference
  Authors
Chudnovsky Y, Khavari PA, Adams AE.
  Title
Melanoma genetics and the development of rational therapeutics.
  Journal
J Clin Invest 115:813-24 (2005)
DOI:10.1172/JCI24808
Reference
  Authors
Merlino G.
  Title
Cancer biology: the weakest link?
  Journal
Nature 436:33-5 (2005)
DOI:10.1038/436033a
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
Nature 436:117-22 (2005)
DOI:10.1038/nature03664
Reference
  Authors
Levy C, Khaled M, Fisher DE.
  Title
MITF: master regulator of melanocyte development and melanoma oncogene.
  Journal
Trends Mol Med 12:406-14 (2006)
DOI:10.1016/j.molmed.2006.07.008
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
J Invest Dermatol 122:337-41 (2004)
DOI:10.1046/j.0022-202X.2004.22243.x
Reference
  Authors
Gruss C, Herlyn M.
  Title
Role of cadherins and matrixins in melanoma.
  Journal
Curr Opin Oncol 13:117-23 (2001)
DOI:10.1097/00001622-200103000-00006
Reference
  Authors
Thompson JF, Scolyer RA, Kefford RF.
  Title
Cutaneous melanoma.
  Journal
Lancet 365:687-701 (2005)
DOI:10.1016/S0140-6736(05)17951-3
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
Tumour Biol 25:200-7 (2004)
DOI:10.1159/000081103
Reference
  Authors
Lazar-Molnar E, Hegyesi H, Toth S, Falus A.
  Title
Autocrine and paracrine regulation by cytokines and growth factors in melanoma.
  Journal
Cytokine 12:547-54 (2000)
DOI:10.1006/cyto.1999.0614
Related
pathway
pteh04010  MAPK signaling pathway
pteh04110  Cell cycle
pteh04115  p53 signaling pathway
pteh04151  PI3K-Akt signaling pathway
pteh04520  Adherens junction
pteh04916  Melanogenesis
KO pathway
ko05218   
LinkDB

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