KEGG   PATHWAY: biu05218
Entry
biu05218                    Pathway                                
Name
Melanoma - Bos indicus (zebu cattle)
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
biu05218  Melanoma
biu05218

Organism
Bos indicus (zebu cattle) [GN:biu]
Gene
109562156  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
109570879  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
109565142  FGF7; fibroblast growth factor 7 [KO:K04358]
109554256  fibroblast growth factor 4-like [KO:K04358]
109553379  FGF20; fibroblast growth factor 20 [KO:K04358]
109579084  FGF8; fibroblast growth factor 8 [KO:K04358]
109567047  FGF9; fibroblast growth factor 9 [KO:K04358]
109575026  FGF18; fibroblast growth factor 18 [KO:K04358]
109575038  FGF10; fibroblast growth factor 10 [KO:K04358]
109555562  FGF16; fibroblast growth factor 16 [KO:K04358]
109559742  FGF6; fibroblast growth factor 6 [KO:K04358]
109561058  FGF22; fibroblast growth factor 22 [KO:K04358]
109554150  FGF19; fibroblast growth factor 19 [KO:K22603]
109572074  FGF21; fibroblast growth factor 21 [KO:K22429]
109559743  FGF23; fibroblast growth factor 23 [KO:K22428]
109557878  HGF; hepatocyte growth factor [KO:K05460]
109559448  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
109578611  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
109558630  LOW QUALITY PROTEIN: platelet-derived growth factor subunit B-like [KO:K17386]
109559825  platelet-derived growth factor subunit B isoform X1 [KO:K17386]
109571395  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
109569805  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
109559983  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
109553304  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
109557411  MET; LOW QUALITY PROTEIN: hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
109575129  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
109560475  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
109562197  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
109576048  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
109560940  GTPase HRas-like [KO:K02833]
109559581  KRAS; GTPase KRas isoform X1 [KO:K07827]
109555890  NRAS; GTPase NRas [KO:K07828]
109555027  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
109557698  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
109576053  RAF1; LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
109564697  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109561751  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109578667  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109570973  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109554439  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
109559308  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
109559805  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109570415  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109557823  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
109574805  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
109561418  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109556345  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109572496  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109570286  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109554386  BAD; bcl2-associated agonist of cell death [KO:K02158]
109552991  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]
109562627  tumor suppressor ARF-like isoform X1 [KO:K06621]
109558399  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
109574238  TP53; cellular tumor antigen p53 [KO:K04451]
109577247  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
109558203  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
109566987  RB1; retinoblastoma-associated protein [KO:K06618]
109567683  E2F1; transcription factor E2F1 [KO:K17454]
109576116  E2F2; transcription factor E2F2 [KO:K09389]
109577245  E2F3; transcription factor E2F3 [KO:K06620]
109572856  cadherin-1 [KO:K05689]
109561788  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
109556176  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
109563283  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
109571977  apoptosis regulator BAX [KO:K02159]
109571778  BAX; apoptosis regulator BAX [KO:K02159]
109577301  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
109569541  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
109564642  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
109576163  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
biu04010  MAPK signaling pathway
biu04110  Cell cycle
biu04115  p53 signaling pathway
biu04151  PI3K-Akt signaling pathway
biu04520  Adherens junction
biu04916  Melanogenesis
KO pathway
ko05218   
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