KEGG   PATHWAY: pgig05218
Entry
pgig05218                   Pathway                                
Name
Melanoma - Pteropus giganteus (Indian flying fox)
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
pgig05218  Melanoma
pgig05218

Organism
Pteropus giganteus (Indian flying fox) [GN:pgig]
Gene
120581479  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
120616271  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
120591936  FGF16; fibroblast growth factor 16 [KO:K04358]
120602936  FGF9; fibroblast growth factor 9 [KO:K04358]
120614279  FGF10; fibroblast growth factor 10 [KO:K04358]
120614873  FGF18; fibroblast growth factor 18 [KO:K04358]
120583667  FGF22; fibroblast growth factor 22 [KO:K04358]
120583832  FGF20; fibroblast growth factor 20 [KO:K04358]
120606452  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
120584645  FGF4; fibroblast growth factor 4 [KO:K04358]
120607305  FGF6; fibroblast growth factor 6 [KO:K04358]
120588259  FGF5; fibroblast growth factor 5 [KO:K04358]
120609690  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
120623126  FGF7; fibroblast growth factor 7 [KO:K04358]
120584636  FGF19; fibroblast growth factor 19 [KO:K22603]
120606965  FGF21; fibroblast growth factor 21 [KO:K22429]
120607306  FGF23; fibroblast growth factor 23 [KO:K22428]
120591565  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
120614955  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
120615920  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
120603004  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
120613440  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
120599685  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
120591156  EGF; pro-epidermal growth factor [KO:K04357]
120595650  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
120601224  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
120587362  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
120588066  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
120581545  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
120602477  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
120584662  HRAS; GTPase HRas isoform X1 [KO:K02833]
120618351  KRAS; GTPase KRas isoform X1 [KO:K07827]
120585069  NRAS; GTPase NRas isoform X1 [KO:K07828]
120605533  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
120601203  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
120621476  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
120604492  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
120615382  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
120606851  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
120620121  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120584714  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
120604974  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
120582132  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
120596984  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
120585845  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
120606549  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
120608247  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
120620206  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
120613959  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120595669  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120619079  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120600645  BAD; bcl2-associated agonist of cell death [KO:K02158]
120609356  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]
120617114  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
120605043  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
120589680  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
120597553  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
120615024  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
120583848  RB1; retinoblastoma-associated protein [KO:K06618]
120603555  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
120596256  E2F2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
120596257  transcription factor E2F2-like [KO:K09389]
120605571  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
120593865  CDH1; cadherin-1 [KO:K05689]
120583203  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
120594128  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
120583737  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
120606950  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
120597665  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
120607230  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
120598501  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
120593791  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
Compound
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:16822996
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
DOI:10.1056/NEJMra052166
Reference
PMID:12894244
  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
PMID:16750612
  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
PMID:15841168
  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
PMID:16001050
  Authors
Merlino G.
  Title
Cancer biology: the weakest link?
  Journal
Nature 436:33-5 (2005)
DOI:10.1038/436033a
Reference
PMID:16001072
  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
PMID:16899407
  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
PMID:15009714
  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
PMID:11224709
  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
PMID:15721476
  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
PMID:14695152
  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
PMID:15557758
  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
PMID:10843728
  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
pgig04010  MAPK signaling pathway
pgig04110  Cell cycle
pgig04115  p53 signaling pathway
pgig04151  PI3K-Akt signaling pathway
pgig04520  Adherens junction
pgig04916  Melanogenesis
KO pathway
ko05218   
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