KEGG   PATHWAY: mcc05218Help
Entry
mcc05218                    Pathway                                

Name
Melanoma - Macaca mulatta (rhesus monkey)
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; Cancers
BRITE hierarchy
Pathway map
Melanoma
mcc05218

All organismsOrtholog table
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
705970  
FGF1; fibroblast growth factor 1 (acidic) [KO:K18496]
574136  
FGF2; fibroblast growth factor 2 (basic) [KO:K18497]
715564  
FGF11; fibroblast growth factor 11 [KO:K04358]
710643  
FGF23; fibroblast growth factor 23 [KO:K04358]
710739  
FGF6; fibroblast growth factor 6 [KO:K04358]
695460  
FGF13; fibroblast growth factor 13 [KO:K04358]
574345  
FGF7; fibroblast growth factor 7 [KO:K04358]
701584  
FGF10; fibroblast growth factor 10 [KO:K04358]
705612  
FGF16; fibroblast growth factor 16 [KO:K04358]
702727  
FGF22; fibroblast growth factor 22 [KO:K04358]
705813  
FGF12; fibroblast growth factor 12 [KO:K04358]
701847  
FGF20; fibroblast growth factor 20 [KO:K04358]
714199  
fibroblast growth factor 8-like; K04358 fibroblast growth factor [KO:K04358]
708918  
FGF3; fibroblast growth factor 3 [KO:K04358]
709016  
FGF4; fibroblast growth factor 4 [KO:K04358]
709109  
FGF19; fibroblast growth factor 19 [KO:K04358]
706659  
FGF17; fibroblast growth factor 17 [KO:K04358]
718288  
FGF21; fibroblast growth factor 21 [KO:K04358]
721324  
uncharacterized LOC721324; K04358 fibroblast growth factor [KO:K04358]
701077  
FGF14; fibroblast growth factor 14 [KO:K04358]
706418  
FGF13; fibroblast growth factor 13-like [KO:K04358]
695896  
FGF5; fibroblast growth factor 5 [KO:K04358]
702072  
fibroblast growth factor 18-like; K04358 fibroblast growth factor [KO:K04358]
708316  
HGF; hepatocyte growth factor (hepapoietin A [KO:K05460]
698444  
IGF1; insulin-like growth factor 1 (somatomedin C) [KO:K05459]
707725  
PDGFA; platelet-derived growth factor alpha polypeptide [KO:K04359]
703173  
PDGFB; platelet-derived growth factor beta polypeptide [KO:K17386]
704310  
PDGFD; platelet derived growth factor D [KO:K05450]
700236  
PDGFC; platelet derived growth factor C [KO:K05450]
698619  
EGF; epidermal growth factor [KO:K04357]
700126  
FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
704562  
MET; met proto-oncogene (hepatocyte growth factor receptor) [KO:K05099] [EC:2.7.10.1]
708227  
IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
697002  
PDGFRA; alpha-type platelet-derived growth factor receptor-like [KO:K04363] [EC:2.7.10.1]
711353  
PDGFRB; platelet-derived growth factor receptor, beta polypeptide [KO:K05089] [EC:2.7.10.1]
613027  
EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
698830  
HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
707977  
KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
709089  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
707169  
ARAF; v-raf murine sarcoma 3611 viral oncogene homolog [KO:K08845] [EC:2.7.11.1]
693554  
serine/threonine-protein kinase B-raf-like; K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] [KO:K04365] [EC:2.7.11.1]
694725  
RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
710415  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
721821  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
698569  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
708938  
MAPK3; mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
715650  
CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
698857  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
716098  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
709959  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
707310  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
719367  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
722027  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
698996  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
714717  
AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
697747  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
700591  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
717740  
BAD; BCL2-associated agonist of cell death [KO:K02158]
705121  
PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.67 3.1.3.48 3.1.3.16]
709988  
cyclin-dependent kinase inhibitor 2A; K06621 cyclin-dependent kinase inhibitor 2A [KO:K06621]
718284  
MDM2; Mdm2, p53 E3 ubiquitin protein ligase homolog (mouse) [KO:K06643] [EC:6.3.2.19]
716170  
TP53; tumor protein p53 [KO:K04451]
719199  
CDKN1A; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [KO:K06625]
574320  
CCND1; G1/S-specific cyclin-D1 [KO:K04503]
701822  
CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
704871  
RB1; retinoblastoma 1 [KO:K06618]
714126  
E2F1; E2F transcription factor 1 [KO:K17454]
710200  
E2F2; E2F transcription factor 2 [KO:K09389]
713904  
transcription factor E2F3-like; K06620 transcription factor E2F3 [KO:K06620]
704387  
CDH1; cadherin-1-like [KO:K05689]
695537  
MITF; microphthalmia-associated transcription factor [KO:K09455]
Compound
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Miller AJ, Mihm MC Jr.
  Title
Melanoma.
  Journal
N Engl J Med 355:51-65 (2006)
Reference
  Authors
Chin L.
  Title
The genetics of malignant melanoma: lessons from mouse and man.
  Journal
Nat Rev Cancer 3:559-70 (2003)
Reference
  Authors
Takata M, Saida T.
  Title
Genetic alterations in melanocytic tumors.
  Journal
J Dermatol Sci 43:1-10 (2006)
Reference
  Authors
Chudnovsky Y, Khavari PA, Adams AE.
  Title
Melanoma genetics and the development of rational therapeutics.
  Journal
J Clin Invest 115:813-24 (2005)
Reference
  Authors
Merlino G.
  Title
Cancer biology: the weakest link?
  Journal
Nature 436:33-5 (2005)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  Authors
Gruss C, Herlyn M.
  Title
Role of cadherins and matrixins in melanoma.
  Journal
Curr Opin Oncol 13:117-23 (2001)
Reference
  Authors
Thompson JF, Scolyer RA, Kefford RF.
  Title
Cutaneous melanoma.
  Journal
Lancet 365:687-701 (2005)
Reference
  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
  Authors
Hussein MR.
  Title
The TP53 tumor suppressor gene and melanoma tumorigenesis: is there a relationship?
  Journal
Tumour Biol 25:200-7 (2004)
Reference
  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)
KO pathway
 

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