KEGG   PATHWAY: pale05218
Entry
pale05218                   Pathway                                
Name
Melanoma - Pteropus alecto (black flying fox)
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
pale05218  Melanoma
pale05218

Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102894192  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
107196088  FGF2; fibroblast growth factor 2 [KO:K18497]
102895922  FGF10; fibroblast growth factor 10 [KO:K04358]
102887777  FGF7; fibroblast growth factor 7 [KO:K04358]
102892141  FGF6; fibroblast growth factor 6 [KO:K04358]
102895642  FGF5; fibroblast growth factor 5 [KO:K04358]
102890153  FGF16; fibroblast growth factor 16 [KO:K04358]
102893226  FGF8; fibroblast growth factor 8 isoform X4 [KO:K04358]
102894115  FGF18; fibroblast growth factor 18 [KO:K04358]
102888098  FGF20; fibroblast growth factor 20 [KO:K04358]
102893244  FGF4; fibroblast growth factor 4 [KO:K04358]
102894279  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
102887882  FGF9; fibroblast growth factor 9 [KO:K04358]
102896895  FGF22; fibroblast growth factor 22 [KO:K04358]
102885081  FGF19; fibroblast growth factor 19 [KO:K22603]
102886540  FGF21; fibroblast growth factor 21 [KO:K22429]
102883346  FGF23; fibroblast growth factor 23 [KO:K22428]
102884470  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
102890331  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
102893670  PDGFA; platelet-derived growth factor subunit A [KO:K04359]
102897699  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
102894123  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
102890668  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
102891552  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102898943  FGFR1; fibroblast growth factor receptor 1 isoform X9 [KO:K04362] [EC:2.7.10.1]
102885990  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
102885962  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
102895362  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
102887643  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
102893495  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102896270  HRAS; GTPase HRas isoform X3 [KO:K02833]
102895590  KRAS; GTPase KRas isoform X1 [KO:K07827]
102885950  NRAS; GTPase NRas isoform X2 [KO:K07828]
102877877  ARAF; serine/threonine-protein kinase A-Raf isoform X2 [KO:K08845] [EC:2.7.11.1]
102878393  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102897122  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102879034  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102895390  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102885749  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102885330  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102894222  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102891637  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102877892  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
102881949  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]
102896422  LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 2A [KO:K06621]
102884281  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
102889604  TP53; cellular tumor antigen p53 [KO:K04451]
102894049  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102896272  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102893019  RB1; retinoblastoma-associated protein [KO:K06618]
102895276  E2F1; transcription factor E2F1 [KO:K17454]
102884459  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
102887239  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102886394  CDH1; cadherin-1 isoform X1 [KO:K05689]
102886440  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102878191  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102885790  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102885135  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
102883540  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
102879479  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
102890888  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
102899015  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
pale04010  MAPK signaling pathway
pale04110  Cell cycle
pale04115  p53 signaling pathway
pale04151  PI3K-Akt signaling pathway
pale04520  Adherens junction
pale04916  Melanogenesis
KO pathway
ko05218   
LinkDB

DBGET integrated database retrieval system