KEGG   PATHWAY: cfr05218
Entry
cfr05218                    Pathway                                
Name
Melanoma - Camelus ferus (Wild Bactrian camel)
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
cfr05218  Melanoma
cfr05218

Organism
Camelus ferus (Wild Bactrian camel) [GN:cfr]
Gene
102513829  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
102523878  FGF9; fibroblast growth factor 9 isoform X5 [KO:K04358]
102523201  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
102506593  FGF6; fibroblast growth factor 6 [KO:K04358]
102522544  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
102506811  FGF8; fibroblast growth factor 8 [KO:K04358]
102520066  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
102513465  FGF10; fibroblast growth factor 10 [KO:K04358]
102506716  FGF16; fibroblast growth factor 16 [KO:K04358]
102524081  FGF18; fibroblast growth factor 18 isoform X1 [KO:K04358]
102519120  FGF7; fibroblast growth factor 7 [KO:K04358]
102504464  FGF20; fibroblast growth factor 20 [KO:K04358]
116666646  FGF4; fibroblast growth factor 4 [KO:K04358]
116666647  FGF3; fibroblast growth factor 3 [KO:K04358]
102514176  FGF21; fibroblast growth factor 21 [KO:K22429]
102510802  FGF23; fibroblast growth factor 23 [KO:K22428]
102515749  HGF; hepatocyte growth factor isoform X2 [KO:K05460]
102506236  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
102520052  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
102509299  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
102508964  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
102515439  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
102523769  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102515264  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
102504138  hepatocyte growth factor receptor isoform X3 [KO:K05099] [EC:2.7.10.1]
102524338  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
102512589  PDGFRA; LOW QUALITY PROTEIN: platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
102512951  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
102504272  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102524334  HRAS; GTPase HRas isoform X1 [KO:K02833]
102516372  KRAS; GTPase KRas isoform X1 [KO:K07827]
102509562  NRAS; GTPase NRas [KO:K07828]
102506774  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
102524100  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
102517521  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102515937  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102511209  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102517586  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102521659  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102518309  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102522300  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102523502  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102518643  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102519994  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102513205  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102505690  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102520923  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102503460  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102515350  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102519101  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
106729149  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102523295  BAD; bcl2-associated agonist of cell death isoform X2 [KO:K02158]
102515104  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]
102517211  cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
102522420  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
102524476  TP53; cellular tumor antigen p53 [KO:K04451]
102509404  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
102520456  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
102516870  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
102517851  E2F1; transcription factor E2F1 [KO:K17454]
102515523  E2F2; transcription factor E2F2 [KO:K09389]
102513737  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102518832  cadherin-1 isoform X2 [KO:K05689]
102516207  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102508482  GADD45A; LOW QUALITY PROTEIN: growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
116660720  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102512073  ferritin light chain isoform X1 [KO:K02159]
102513729  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
102523860  DDB2; DNA damage-binding protein 2 isoform X4 [KO:K10140]
102507560  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
102513508  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
cfr04010  MAPK signaling pathway
cfr04110  Cell cycle
cfr04115  p53 signaling pathway
cfr04151  PI3K-Akt signaling pathway
cfr04520  Adherens junction
cfr04916  Melanogenesis
KO pathway
ko05218   
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