KEGG   PATHWAY: ko05211Help
ko05211                     Pathway                                

Renal cell carcinoma
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.
09160 Human Diseases; 09161 Cancers
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ko05211  Renal cell carcinoma

Ortholog table
M00383  ECV complex [PATH:ko05211]
H00021  Renal cell carcinoma
H00559  von Hippel-Lindau syndrome
K08268  hypoxia-inducible factor 1 alpha
K09095  hypoxia-inducible factor 2 alpha
K09592  hypoxia-inducible factor prolyl hydroxylase [EC:]
K03871  von Hippel-Lindau disease tumor supressor
K03872  transcription elongation factor B, polypeptide 1
K03873  transcription elongation factor B, polypeptide 2
K03868  RING-box protein 1 [EC:]
K03870  cullin 2
K09097  aryl hydrocarbon receptor nuclear translocator
K15589  aryl hydrocarbon receptor nuclear translocator 2
K04498  E1A/CREB-binding protein [EC:]
K07299  MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
K05448  vascular endothelial growth factor A
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K13377  transforming growth factor beta-3
K17386  platelet-derived growth factor subunit B
K08774  transforming growth factor, alpha
K05460  hepatocyte growth factor
K05099  proto-oncogene tyrosine-protein kinase Met [EC:]
K09593  GRB2-associated-binding protein 1
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:]
K02158  Bcl-2-antagonist of cell death
K04438  proto-oncogene C-crk
K06277  Rap guanine nucleotide exchange factor 1
K04353  Ras-related protein Rap-1A
K07836  Ras-related protein Rap-1B
K07293  tyrosine-protein phosphatase non-receptor type 11 [EC:]
K04364  growth factor receptor-binding protein 2
K03099  son of sevenless
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K08845  A-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04369  mitogen-activated protein kinase kinase 2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K02678  C-ets-1
K04448  transcription factor AP-1
K04392  Ras-related C3 botulinum toxin substrate 1
K04393  cell division control protein 42
K04409  p21-activated kinase 1 [EC:]
K04410  p21-activated kinase 2 [EC:]
K05733  p21-activated kinase 3 [EC:]
K05734  p21-activated kinase 4 [EC:]
K05736  p21-activated kinase 5 [EC:]
K05735  p21-activated kinase 6 [EC:]
K13105  proline-rich protein PRCC
K09105  transcription factor E3
K06625  cyclin-dependent kinase inhibitor 1A
K01679  fumarate hydratase, class II [EC:]
K09594  folliculin
C00007  Oxygen
C00122  Fumarate
C00149  (S)-Malate
Cohen HT, McGovern FJ.
Renal-cell carcinoma.
N Engl J Med 353:2477-90 (2005)
Pavlovich CP, Schmidt LS.
Searching for the hereditary causes of renal-cell carcinoma.
Nat Rev Cancer 4:381-93 (2004)
Linehan WM, Walther MM, Zbar B.
The genetic basis of cancer of the kidney.
J Urol 170:2163-72 (2003)
Kim WY, Kaelin WG.
Role of VHL gene mutation in human cancer.
J Clin Oncol 22:4991-5004 (2004)
Sudarshan S, Linehan WM, Neckers L.
HIF and fumarate hydratase in renal cancer.
Br J Cancer 96:403-7 (2007)
Sudarshan S, Pinto PA, Neckers L, Linehan WM.
Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer.
Nat Clin Pract Urol 4:104-10 (2007)
Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF.
Met, metastasis, motility and more.
Nat Rev Mol Cell Biol 4:915-25 (2003)
Muller-Hocker J, Babaryka G, Schmid I, Jung A
Overexpression of cyclin D1, D3, and p21 in an infantile renal carcinoma with Xp11.2 TFE3-gene fusion.
Pathol Res Pract 204:589-97 (2008)
Bodmer D, van den Hurk W, van Groningen JJ, Eleveld MJ, Martens GJ, Weterman MA, van Kessel AG.
Understanding familial and non-familial renal cell cancer.
Hum Mol Genet 11:2489-98 (2002)
Kauffman EC, Ricketts CJ, Rais-Bahrami S, Yang Y, Merino MJ, Bottaro DP, Srinivasan R, Linehan WM
Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers.
Nat Rev Urol 11:465-75 (2014)
Skalsky YM, Ajuh PM, Parker C, Lamond AI, Goodwin G, Cooper CS
PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors.
Oncogene 20:178-87 (2001)
Medendorp K, van Groningen JJ, Vreede L, Hetterschijt L, Brugmans L, van den Hurk WH, van Kessel AG
The renal cell carcinoma-associated oncogenic fusion protein PRCCTFE3 provokes p21 WAF1/CIP1-mediated cell cycle delay.
Exp Cell Res 315:2399-409 (2009)
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