KEGG   PATHWAY: pon05218
Entry
pon05218                    Pathway                                

Name
Melanoma - Pongo abelii (Sumatran orangutan)
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
pon05218  Melanoma
pon05218

Organism
Pongo abelii (Sumatran orangutan) [GN:pon]
Gene
100174103  FGF1; fibroblast growth factor 1 [KO:K18496]
100459751  FGF2; fibroblast growth factor 2 [KO:K18497]
100454905  FGF16; fibroblast growth factor 16 [KO:K04358]
100448388  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
100454475  FGF9; fibroblast growth factor 9 [KO:K04358]
100460891  FGF20; fibroblast growth factor 20 [KO:K04358]
100450364  FGF17; fibroblast growth factor 17 isoform X2 [KO:K04358]
100440363  FGF3; fibroblast growth factor 3 [KO:K04358]
100440732  FGF4; fibroblast growth factor 4 [KO:K04358]
100459069  FGF6; fibroblast growth factor 6 [KO:K04358]
100432789  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
100437858  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
100460498  FGF18; fibroblast growth factor 18 [KO:K04358]
100172539  FGF7; fibroblast growth factor 7 precursor [KO:K04358]
100431992  FGF10; fibroblast growth factor 10 [KO:K04358]
100441475  FGF19; fibroblast growth factor 19 [KO:K22603]
100447289  FGF21; fibroblast growth factor 21 [KO:K22429]
100439010  FGF23; fibroblast growth factor 23 [KO:K22428]
100462115  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
100444645  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
100440212  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
100460243  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
100437861  PDGFC; platelet-derived growth factor C [KO:K05450]
100172718  PDGFD; platelet-derived growth factor D precursor [KO:K05450]
100455021  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
100174545  FGFR1; fibroblast growth factor receptor 1 precursor [KO:K04362] [EC:2.7.10.1]
100137030  MET; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
100172156  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
100431735  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
100460001  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
100459280  EGFR; epidermal growth factor receptor isoform X2 [KO:K04361] [EC:2.7.10.1]
100459427  HRAS; GTPase HRas [KO:K02833]
100462513  KRAS; GTPase KRas isoform X1 [KO:K07827]
100174317  NRAS; GTPase NRas precursor [KO:K07828]
100431871  ARAF; serine/threonine-protein kinase A-Raf isoform X4 [KO:K08845] [EC:2.7.11.1]
100442288  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100173732  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
100446021  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100450988  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100169740  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100431824  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100171625  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100443314  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
100432846  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100453779  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103889133  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100174298  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100173589  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100437617  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100454279  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100448114  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100442100  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100454097  BAD; bcl2-associated agonist of cell death [KO:K02158]
100171828  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
100461015  cyclin-dependent kinase inhibitor 2A [KO:K06621]
100171532  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
100435218  TP53; cellular tumor antigen p53 [KO:K04451]
100453682  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100454924  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100462155  RB1; retinoblastoma-associated protein [KO:K06618]
100435851  E2F1; transcription factor E2F1 [KO:K17454]
100458002  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
100448297  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
100174439  CDH1; cadherin-1 precursor [KO:K05689]
100436665  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100452809  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100456437  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100450682  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100460189  bcl-2 homologous antagonist/killer [KO:K14021]
100432001  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
100454099  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
100443121  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
100172074  MITF; microphthalmia-associated transcription factor isoform X3 [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
pon04010  MAPK signaling pathway
pon04110  Cell cycle
pon04115  p53 signaling pathway
pon04151  PI3K-Akt signaling pathway
pon04520  Adherens junction
pon04916  Melanogenesis
KO pathway
ko05218   
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