KEGG   PATHWAY: ppam05218
Entry
ppam05218                   Pathway                                
Name
Melanoma - Pteronotus mesoamericanus (Parnell's mustached bat)
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
ppam05218  Melanoma
ppam05218

Organism
Pteronotus mesoamericanus (Parnell's mustached bat) [GN:ppam]
Gene
129066585  FGF1; fibroblast growth factor 1 [KO:K18496]
129061435  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
129068332  FGF4; fibroblast growth factor 4 [KO:K04358]
129068458  FGF3; fibroblast growth factor 3 [KO:K04358]
129074873  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
129082327  FGF9; fibroblast growth factor 9 [KO:K04358]
129077291  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
129064258  FGF7; fibroblast growth factor 7 [KO:K04358]
129084108  FGF5; fibroblast growth factor 5 [KO:K04358]
129064694  FGF20; fibroblast growth factor 20 [KO:K04358]
129065350  FGF16; fibroblast growth factor 16 [KO:K04358]
129071959  FGF10; fibroblast growth factor 10 [KO:K04358]
129072488  FGF22; LOW QUALITY PROTEIN: fibroblast growth factor 22 [KO:K04358]
129066345  FGF18; fibroblast growth factor 18 [KO:K04358]
129074224  FGF6; fibroblast growth factor 6 [KO:K04358]
129068333  FGF19; fibroblast growth factor 19 [KO:K22603]
129082796  FGF21; fibroblast growth factor 21 [KO:K22429]
129074223  FGF23; fibroblast growth factor 23 [KO:K22428]
129063396  HGF; hepatocyte growth factor [KO:K05460]
129071377  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
129065324  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
129077932  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
129072575  PDGFC; platelet-derived growth factor C [KO:K05450]
129086014  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
129085287  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
129064807  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
129063382  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
129061268  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
129077631  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
129066549  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
129068919  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
129073113  HRAS; GTPase HRas isoform X1 [KO:K02833]
129084969  KRAS; GTPase KRas isoform X1 [KO:K07827]
129063946  NRAS; GTPase NRas [KO:K07828]
129065223  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
129062984  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
129088423  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129064157  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129078155  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129078069  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129086248  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129068523  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
129075823  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
129075675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129076577  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129088291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129074969  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129069407  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129074590  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129076641  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129066231  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129073033  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129068612  BAD; bcl2-associated agonist of cell death [KO:K02158]
129069750  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]
129075868  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
129072290  TP53; cellular tumor antigen p53 [KO:K04451]
129067419  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
129063507  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
129080865  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
129070474  E2F1; transcription factor E2F1 [KO:K17454]
129068981  E2F2; transcription factor E2F2 [KO:K09389]
129085787  E2F3; transcription factor E2F3 [KO:K06620]
129075248  CDH1; cadherin-1 [KO:K05689]
129082291  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
129069921  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
129081112  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
129082924  BAX; apoptosis regulator BAX [KO:K02159]
129066993  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
129081434  DDB2; DNA damage-binding protein 2 [KO:K10140]
129074622  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
129088216  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
ppam04010  MAPK signaling pathway
ppam04110  Cell cycle
ppam04115  p53 signaling pathway
ppam04151  PI3K-Akt signaling pathway
ppam04520  Adherens junction
ppam04916  Melanogenesis
KO pathway
ko05218   
LinkDB

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