KEGG   PATHWAY: tfn05218
Entry
tfn05218                    Pathway                                
Name
Melanoma - Trachypithecus francoisi (Francois's langur)
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
tfn05218  Melanoma
tfn05218

Organism
Trachypithecus francoisi (Francois's langur) [GN:tfn]
Gene
117065686  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
117085877  FGF2; fibroblast growth factor 2 [KO:K18497]
117079898  FGF3; fibroblast growth factor 3 [KO:K04358]
117070685  FGF7; fibroblast growth factor 7 [KO:K04358]
117080722  FGF4; fibroblast growth factor 4 [KO:K04358]
117090673  FGF6; fibroblast growth factor 6 [KO:K04358]
117065085  FGF10; fibroblast growth factor 10 [KO:K04358]
117074128  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
117092120  FGF20; fibroblast growth factor 20 [KO:K04358]
117065449  FGF18; fibroblast growth factor 18 [KO:K04358]
117074964  FGF9; fibroblast growth factor 9 [KO:K04358]
117092974  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
117085405  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
117067885  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
117077528  FGF16; fibroblast growth factor 16 [KO:K04358]
117080426  FGF19; fibroblast growth factor 19 [KO:K22603]
117093783  FGF21; fibroblast growth factor 21 [KO:K22429]
117090674  FGF23; fibroblast growth factor 23 [KO:K22428]
117072632  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
117089531  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
117072614  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
117096471  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
117080013  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
117085785  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
117094867  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
117073436  MET; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
117070145  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
117085606  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
117065596  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
117073506  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
117081688  HRAS; GTPase HRas isoform X1 [KO:K02833]
117074634  NRAS; GTPase NRas [KO:K07828]
117078298  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
117072297  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
117083269  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
117084479  LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
117070473  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117076490  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
117087606  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
117096627  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117081518  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
117089862  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
117083761  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117084122  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
117093348  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117065206  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117092662  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
117075022  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
117071286  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117091956  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117076331  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117080612  BAD; bcl2-associated agonist of cell death [KO:K02158]
117086074  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]
117098660  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
117089769  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
117067758  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
117087134  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
117073473  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
117063258  RB1; retinoblastoma-associated protein [KO:K06618]
117068658  E2F1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
117093139  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
117086783  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
117087958  CDH1; cadherin-1 isoform X1 [KO:K05689]
117098362  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
117092072  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
117075703  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
117091541  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
117087056  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
117096195  bcl-2 homologous antagonist/killer-like [KO:K14021]
117080146  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
117065273  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
117083122  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
tfn04010  MAPK signaling pathway
tfn04110  Cell cycle
tfn04115  p53 signaling pathway
tfn04151  PI3K-Akt signaling pathway
tfn04520  Adherens junction
tfn04916  Melanogenesis
KO pathway
ko05218   
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