KEGG PATHWAY: hsa05218

PATHWAY: hsa05218

Entry

hsa05218 Pathway

Name

Melanoma - Homo sapiens (human)

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

Pathway map

hsa05218

Melanoma

Disease

H00038

Malignant melanoma

Drug

D09996	Vemurafenib (USAN/INN)
D10064	Dabrafenib (USAN)
D10104	Dabrafenib mesylate (USAN)

Organism

Homo sapiens (human) [GN:hsa]

Gene

2246	FGF1; fibroblast growth factor 1 (acidic) [KO:K04358]
2247	FGF2; fibroblast growth factor 2 (basic) [KO:K04358]
2248	FGF3; fibroblast growth factor 3 [KO:K04358]
2249	FGF4; fibroblast growth factor 4 [KO:K04358]
8822	FGF17; fibroblast growth factor 17 [KO:K04358]
2251	FGF6; fibroblast growth factor 6 [KO:K04358]
2252	FGF7; fibroblast growth factor 7 [KO:K04358]
2253	FGF8; fibroblast growth factor 8 (androgen-induced) [KO:K04358]
2254	FGF9; fibroblast growth factor 9 (glia-activating factor) [KO:K04358]
2255	FGF10; fibroblast growth factor 10 [KO:K04358]
2256	FGF11; fibroblast growth factor 11 [KO:K04358]
2257	FGF12; fibroblast growth factor 12 [KO:K04358]
2258	FGF13; fibroblast growth factor 13 [KO:K04358]
2259	FGF14; fibroblast growth factor 14 [KO:K04358]
8823	FGF16; fibroblast growth factor 16 [KO:K04358]
2250	FGF5; fibroblast growth factor 5 [KO:K04358]
8817	FGF18; fibroblast growth factor 18 [KO:K04358]
9965	FGF19; fibroblast growth factor 19 [KO:K04358]
26281	FGF20; fibroblast growth factor 20 [KO:K04358]
26291	FGF21; fibroblast growth factor 21 [KO:K04358]
27006	FGF22; fibroblast growth factor 22 [KO:K04358]
8074	FGF23; fibroblast growth factor 23 [KO:K04358]
3082	HGF; hepatocyte growth factor (hepapoietin A [KO:K05460]
3479	IGF1; insulin-like growth factor 1 (somatomedin C) [KO:K05459]
5155	PDGFB; platelet-derived growth factor beta polypeptide [KO:K04359]
5154	PDGFA; platelet-derived growth factor alpha polypeptide [KO:K04359]
56034	PDGFC; platelet derived growth factor C [KO:K05450]
80310	PDGFD; platelet derived growth factor D [KO:K05450]
1950	EGF; epidermal growth factor [KO:K04357]
2260	FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
4233	MET; met proto-oncogene (hepatocyte growth factor receptor) [KO:K05099] [EC:2.7.10.1]
3480	IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
5156	PDGFRA; platelet-derived growth factor receptor, alpha polypeptide [KO:K04363] [EC:2.7.10.1]
5159	PDGFRB; platelet-derived growth factor receptor, beta polypeptide [KO:K05089] [EC:2.7.10.1]
1956	EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
3265	HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845	KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893	NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
369	ARAF; v-raf murine sarcoma 3611 viral oncogene homolog [KO:K08845] [EC:2.7.11.1]
673	BRAF; v-raf murine sarcoma viral oncogene homolog B1 [KO:K04365] [EC:2.7.11.1]
5894	RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
5604	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605	MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594	MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595	MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
1019	CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
5290	PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293	PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291	PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294	PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503	PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
207	AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
572	BAD; BCL2-associated agonist of cell death [KO:K02158]
5728	PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.67 3.1.3.48 3.1.3.16]
1029	CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
4193	MDM2; MDM2 oncogene, E3 ubiquitin protein ligase [KO:K06643] [EC:6.3.2.19]
7157	TP53; tumor protein p53 [KO:K04451]
1026	CDKN1A; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [KO:K06625]
595	CCND1; cyclin D1 [KO:K04503]
1021	CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
5925	RB1; retinoblastoma 1 [KO:K06618]
1869	E2F1; E2F transcription factor 1 [KO:K06620]
1871	E2F3; E2F transcription factor 3 [KO:K06620]
1870	E2F2; E2F transcription factor 2 [KO:K09389]
999	CDH1; cadherin 1, type 1, E-cadherin (epithelial) [KO:K05689]
4286	MITF; microphthalmia-associated transcription factor [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)

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)

Reference

PMID:16750612

Authors

Takata M, Saida T.

Title

Genetic alterations in melanocytic tumors.

Journal

J Dermatol Sci 43:1-10 (2006)

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)

Reference

PMID:16001050

Authors

Merlino G.

Title

Cancer biology: the weakest link?

Journal

Nature 436:33-5 (2005)

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)

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)

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)

Reference

PMID:11224709

Authors

Gruss C, Herlyn M.

Title

Role of cadherins and matrixins in melanoma.

Journal

Curr Opin Oncol 13:117-23 (2001)

Reference

PMID:15721476

Authors

Thompson JF, Scolyer RA, Kefford RF.

Title

Cutaneous melanoma.

Journal

Lancet 365:687-701 (2005)

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)

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)

KO pathway

ko05218

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Ontology (2)   
   KEGG BRITE (2)   
Pathway (1)   
   BioSystems (1)   
Disease (1)   
   KEGG DISEASE (1)   
Drug (3)   
   KEGG DRUG (3)   
Genome (1)   
   KEGG GENOME (1)   
Gene (71)   
   KEGG GENES (71)   
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