KEGG   PATHWAY: mlk05218
Entry
mlk05218                    Pathway                                
Name
Melanoma - Mustela lutreola (European mink)
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
mlk05218  Melanoma
mlk05218

Organism
Mustela lutreola (European mink) [GN:mlk]
Gene
131832196  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
131828225  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
131836265  FGF7; fibroblast growth factor 7 isoform X1 [KO:K04358]
131839915  FGF6; fibroblast growth factor 6 [KO:K04358]
131834291  FGF17; fibroblast growth factor 17 [KO:K04358]
131819956  FGF5; fibroblast growth factor 5 [KO:K04358]
131820615  FGF20; fibroblast growth factor 20 [KO:K04358]
131813822  FGF9; fibroblast growth factor 9 [KO:K04358]
131821509  FGF16; fibroblast growth factor 16 [KO:K04358]
131822740  FGF4; fibroblast growth factor 4 [KO:K04358]
131822741  FGF3; fibroblast growth factor 3 [KO:K04358]
131823154  FGF22; fibroblast growth factor 22 isoform X1 [KO:K04358]
131830281  FGF8; fibroblast growth factor 8 [KO:K04358]
131831722  FGF10; fibroblast growth factor 10 [KO:K04358]
131831909  FGF18; fibroblast growth factor 18 [KO:K04358]
131822739  FGF19; fibroblast growth factor 19 [KO:K22603]
131818352  FGF21; fibroblast growth factor 21 [KO:K22429]
131838416  FGF23; fibroblast growth factor 23 [KO:K22428]
131829310  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
131839335  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
131819467  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
131839489  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
131834784  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
131831691  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
131829316  EGF; pro-epidermal growth factor [KO:K04357]
131820646  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
131829655  MET; hepatocyte growth factor receptor isoform X1 [KO:K05099] [EC:2.7.10.1]
131835676  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
131824031  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
131831763  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
131829150  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
131818337  HRAS; GTPase HRas isoform X1 [KO:K02833]
131838926  KRAS; GTPase KRas isoform X1 [KO:K07827]
131810307  NRAS; GTPase NRas isoform X1 [KO:K07828]
131810524  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
131821130  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
131829849  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
131824239  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
131835957  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
131823312  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
131811758  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
131820131  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
131817001  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
131838541  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
131809015  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
131824589  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
131824847  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
131823754  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
131832309  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
131810162  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
131837056  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
131815063  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131817507  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
131814653  BAD; bcl2-associated agonist of cell death [KO:K02158]
131828969  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]
131828977  phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN-like isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
131828978  LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN-like [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
131829020  LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN-like [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
131812651  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
131839136  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
131815809  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
131833891  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
131829369  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
131813843  RB1; retinoblastoma-associated protein [KO:K06618]
131807833  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
131809711  E2F2; transcription factor E2F2 [KO:K09389]
131834799  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
131818685  cadherin-1-like [KO:K05689]
131818928  CDH1; cadherin-1 [KO:K05689]
131812894  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
131823251  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
131809793  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
131817775  BAX; apoptosis regulator BAX [KO:K02159]
131834235  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
131812400  DDB2; DNA damage-binding protein 2 [KO:K10140]
131832361  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
131824120  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
mlk04010  MAPK signaling pathway
mlk04110  Cell cycle
mlk04115  p53 signaling pathway
mlk04151  PI3K-Akt signaling pathway
mlk04520  Adherens junction
mlk04916  Melanogenesis
KO pathway
ko05218   
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