KEGG   PATHWAY: hsa05211Help
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
BRITE hierarchy
Pathway map
Renal cell carcinoma
hsa05211

All organismsOrtholog table
Module
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-9 family hypoxia-inducible factor 1 [KO:K09592] [EC:1.14.11.29]
112399  
EGLN3; egl-9 family hypoxia-inducible factor 3 [KO:K09592] [EC:1.14.11.29]
112398  
EGLN2; egl-9 family hypoxia-inducible factor 2 [KO:K09592] [EC:1.14.11.29]
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]
5155  
PDGFB; platelet-derived growth factor beta polypeptide [KO:K17386]
7039  
TGFA; transforming growth factor, alpha [KO:K08774]
3082  
HGF; hepatocyte growth factor (hepapoietin A [KO:K05460]
4233  
MET; MET proto-oncogene, receptor tyrosine kinase [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 [KO:K04456] [EC:2.7.11.1]
1398  
CRK; v-crk avian sarcoma virus CT10 oncogene homolog [KO:K04438]
1399  
CRKL; v-crk avian sarcoma virus CT10 oncogene homolog-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; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
369  
ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  
BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [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 avian erythroblastosis virus E26 oncogene homolog 1 [KO:K02678]
Compound
C00007  
Oxygen
C00122  
Fumarate
C00149  
(S)-Malate
Reference
  Authors
Cohen HT, McGovern FJ.
  Title
Renal-cell carcinoma.
  Journal
N Engl J Med 353:2477-90 (2005)
Reference
  Authors
Pavlovich CP, Schmidt LS.
  Title
Searching for the hereditary causes of renal-cell carcinoma.
  Journal
Nat Rev Cancer 4:381-93 (2004)
Reference
  Authors
Linehan WM, Walther MM, Zbar B.
  Title
The genetic basis of cancer of the kidney.
  Journal
J Urol 170:2163-72 (2003)
Reference
  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
  Authors
Kim WY, Kaelin WG.
  Title
Role of VHL gene mutation in human cancer.
  Journal
J Clin Oncol 22:4991-5004 (2004)
Reference
  Authors
Sudarshan S, Linehan WM, Neckers L.
  Title
HIF and fumarate hydratase in renal cancer.
  Journal
Br J Cancer 96:403-7 (2007)
Reference
  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
  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
 

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