KEGG   PATHWAY: mmur05218
Entry
mmur05218                   Pathway                                
Name
Melanoma - Microcebus murinus (gray mouse lemur)
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
mmur05218  Melanoma
mmur05218

Organism
Microcebus murinus (gray mouse lemur) [GN:mmur]
Gene
105862501  FGF1; fibroblast growth factor 1 [KO:K18496]
105882072  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
105881454  FGF6; fibroblast growth factor 6 [KO:K04358]
105873977  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
105867172  FGF18; fibroblast growth factor 18 [KO:K04358]
105867400  FGF3; fibroblast growth factor 3 [KO:K04358]
105867413  FGF4; fibroblast growth factor 4 [KO:K04358]
105882525  FGF20; fibroblast growth factor 20 [KO:K04358]
105860843  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
105884926  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
105870727  FGF7; fibroblast growth factor 7 [KO:K04358]
105857128  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
105878875  FGF9; fibroblast growth factor 9 [KO:K04358]
105857795  FGF10; fibroblast growth factor 10 [KO:K04358]
105866146  FGF16; fibroblast growth factor 16 [KO:K04358]
105867398  FGF19; fibroblast growth factor 19 [KO:K22603]
105865679  FGF21; fibroblast growth factor 21 [KO:K22429]
105881457  FGF23; fibroblast growth factor 23 [KO:K22428]
105879346  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
105875567  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
105868355  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
105858625  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
105881767  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
105874557  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
105872305  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
105870403  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
105869368  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
105871266  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
105867837  PDGFRA; LOW QUALITY PROTEIN: platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
105858450  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
105877217  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
105874032  HRAS; GTPase HRas [KO:K02833]
105857286  KRAS; GTPase KRas isoform X1 [KO:K07827]
105878710  NRAS; GTPase NRas [KO:K07828]
105862190  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
105873244  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
105882676  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105868083  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105873938  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105870697  mitogen-activated protein kinase 6-like [KO:K04371] [EC:2.7.11.24]
105877796  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105871124  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105867511  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
105877995  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
105862660  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105855821  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105886063  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105881219  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105855026  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105877483  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105861093  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105876768  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105863738  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105878474  BAD; bcl2-associated agonist of cell death [KO:K02158]
105870314  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]
105857697  tensin-1-like isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
105874194  cyclin-dependent kinase inhibitor 2A [KO:K06621]
105884627  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
105877486  TP53; cellular tumor antigen p53 [KO:K04451]
105861439  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105879410  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
105855966  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
105866012  E2F1; transcription factor E2F1 [KO:K17454]
105863547  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105865199  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105858954  CDH1; LOW QUALITY PROTEIN: cadherin-1 [KO:K05689]
105873984  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105876174  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105872856  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105865602  BAX; apoptosis regulator BAX isoform X2 [KO:K02159]
105861442  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
105884857  DDB2; DNA damage-binding protein 2 [KO:K10140]
105881857  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
105883876  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
mmur04010  MAPK signaling pathway
mmur04110  Cell cycle
mmur04115  p53 signaling pathway
mmur04151  PI3K-Akt signaling pathway
mmur04520  Adherens junction
mmur04916  Melanogenesis
KO pathway
ko05218   
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