KEGG PATHWAY: hsa05211

PATHWAY: hsa05211

Entry

hsa05211 Pathway

Name

Renal cell carcinoma - Homo sapiens (human)

Description

Renal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal cancer accounts for 1-4% of cases. RCC is not a single disease, it has several morphological subtypes. Conventional RCC (clear cell RCC) accounts for ~80% of cases, followed by papillary RCC (10-15%), chromophobe RCC (5%), and collecting duct RCC (<1%). Genes potentially involved in sporadic neoplasms of each particular type are VHL, MET, BHD, and FH respectively. In the absence of VHL, hypoxia-inducible factor alpha (HIF-alpha) accumulates, leading to production of several growth factors, including vascular endothelial growth factor and platelet-derived growth factor. Activated MET mediates a number of biological effects including motility, invasion of extracellular matrix, cellular transformation, prevention of apoptosis and metastasis formation. Loss of functional FH leads to accumulation of fumarate in the cell, triggering inhibition of HPH and preventing targeted pVHL-mediated degradation of HIF-alpha. BHD mutations cause the Birt-Hogg-Dube syndrome and its associated chromophobe, hybrid oncocytic, and conventional (clear cell) RCC.

Class

Human Diseases; Cancers

Pathway map

hsa05211

Renal cell carcinoma

Module

hsa_M00383

ECV complex [PATH:hsa05211]

Disease

H00021	Renal cell carcinoma
H00559	von Hippel-Lindau syndrome

Drug

D06272	Sorafenib tosilate (JAN)
D08524	Sorafenib (USAN/INN)

Organism

Homo sapiens (human) [GN:hsa]

Gene

3091	HIF1A; hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) [KO:K08268]
2034	EPAS1; endothelial PAS domain protein 1 [KO:K09095]
54583	EGLN1; egl nine homolog 1 (C. elegans) [KO:K09592] [EC:1.14.11.-]
112399	EGLN3; egl nine homolog 3 (C. elegans) [KO:K09592] [EC:1.14.11.-]
112398	EGLN2; egl nine homolog 2 (C. elegans) [KO:K09592] [EC:1.14.11.-]
7428	VHL; von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase [KO:K03871]
6921	TCEB1; transcription elongation factor B (SIII), polypeptide 1 (15kDa, elongin C) [KO:K03872]
6923	TCEB2; transcription elongation factor B (SIII), polypeptide 2 (18kDa, elongin B) [KO:K03873]
9978	RBX1; ring-box 1, E3 ubiquitin protein ligase [KO:K03868]
8453	CUL2; cullin 2 [KO:K03870]
405	ARNT; aryl hydrocarbon receptor nuclear translocator [KO:K09097]
9915	ARNT2; aryl-hydrocarbon receptor nuclear translocator 2 [KO:K15589]
1387	CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033	EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
6513	SLC2A1; solute carrier family 2 (facilitated glucose transporter), member 1 [KO:K07299]
7422	VEGFA; vascular endothelial growth factor A [KO:K05448]
7040	TGFB1; transforming growth factor, beta 1 [KO:K13375]
7042	TGFB2; transforming growth factor, beta 2 [KO:K13376]
7043	TGFB3; transforming growth factor, beta 3 [KO:K13377]
7039	TGFA; transforming growth factor, alpha [KO:K08774]
3082	HGF; hepatocyte growth factor (hepapoietin A [KO:K05460]
4233	MET; met proto-oncogene (hepatocyte growth factor receptor) [KO:K05099] [EC:2.7.10.1]
2549	GAB1; GRB2-associated binding protein 1 [KO:K09593]
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]
1398	CRK; v-crk sarcoma virus CT10 oncogene homolog (avian) [KO:K04438]
1399	CRKL; v-crk sarcoma virus CT10 oncogene homolog (avian)-like [KO:K04438]
2889	RAPGEF1; Rap guanine nucleotide exchange factor (GEF) 1 [KO:K06277]
5906	RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
5908	RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
5781	PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
2885	GRB2; growth factor receptor-bound protein 2 [KO:K04364]
6654	SOS1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
6655	SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
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]
3725	JUN; jun proto-oncogene [KO:K04448]
5879	RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
998	CDC42; cell division cycle 42 [KO:K04393]
5058	PAK1; p21 protein (Cdc42/Rac)-activated kinase 1 [KO:K04409] [EC:2.7.11.1]
5062	PAK2; p21 protein (Cdc42/Rac)-activated kinase 2 [KO:K04410] [EC:2.7.11.1]
5063	PAK3; p21 protein (Cdc42/Rac)-activated kinase 3 [KO:K05733] [EC:2.7.11.1]
10298	PAK4; p21 protein (Cdc42/Rac)-activated kinase 4 [KO:K05734] [EC:2.7.11.1]
56924	PAK6; p21 protein (Cdc42/Rac)-activated kinase 6 [KO:K05735] [EC:2.7.11.1]
57144	PAK7; p21 protein (Cdc42/Rac)-activated kinase 7 [KO:K05736] [EC:2.7.11.1]
2271	FH; fumarate hydratase [KO:K01679] [EC:4.2.1.2]
201163	FLCN; folliculin [KO:K09594]
2113	ETS1; v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) [KO:K02678]
5155	PDGFB; platelet-derived growth factor beta polypeptide [KO:K04359]

Compound

C00007	Oxygen
C00122	Fumarate
C00149	(S)-Malate

Reference

PMID:16339096

Authors

Cohen HT, McGovern FJ.

Title

Renal-cell carcinoma.

Journal

N Engl J Med 353:2477-90 (2005)

Reference

PMID:15122209

Authors

Pavlovich CP, Schmidt LS.

Title

Searching for the hereditary causes of renal-cell carcinoma.

Journal

Nat Rev Cancer 4:381-93 (2004)

Reference

PMID:14634372

Authors

Linehan WM, Walther MM, Zbar B.

Title

The genetic basis of cancer of the kidney.

Journal

J Urol 170:2163-72 (2003)

Reference

PMID:14685170

Authors

Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF.

Title

Met, metastasis, motility and more.

Journal

Nat Rev Mol Cell Biol 4:915-25 (2003)

Reference

PMID:15611513

Authors

Kim WY, Kaelin WG.

Title

Role of VHL gene mutation in human cancer.

Journal

J Clin Oncol 22:4991-5004 (2004)

Reference

PMID:17211469

Authors

Sudarshan S, Linehan WM, Neckers L.

Title

HIF and fumarate hydratase in renal cancer.

Journal

Br J Cancer 96:403-7 (2007)

Reference

PMID:17287871

Authors

Sudarshan S, Pinto PA, Neckers L, Linehan WM.

Title

Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer.

Journal

Nat Clin Pract Urol 4:104-10 (2007)

Reference

PMID:12351585

Authors

Bodmer D, van den Hurk W, van Groningen JJ, Eleveld MJ, Martens GJ, Weterman MA, van Kessel AG.

Title

Understanding familial and non-familial renal cell cancer.

Journal

Hum Mol Genet 11:2489-98 (2002)

KO pathway

ko05211

All links

Ontology (3)   
   KEGG BRITE (3)   
Pathway (2)   
   KEGG MODULE (1)   
   BioSystems (1)   
Disease (2)   
   KEGG DISEASE (2)   
Drug (2)   
   KEGG DRUG (2)   
Genome (1)   
   KEGG GENOME (1)   
Gene (66)   
   KEGG GENES (66)   
All databases (76)   

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