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Entry
map05211                    Pathway                                

Name
Renal cell carcinoma
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
map05211

All organismsOrtholog table
Module
M00383  
ECV complex [PATH:map05211]
Disease
H00021  
Renal cell carcinoma
H00559  
von Hippel-Lindau syndrome
Reference
  Authors
Cohen HT, McGovern FJ.
  Title
Renal-cell carcinoma.
  Journal
N Engl J Med 353:2477-90 (2005)
DOI:10.1056/NEJMra043172
Reference
  Authors
Pavlovich CP, Schmidt LS.
  Title
Searching for the hereditary causes of renal-cell carcinoma.
  Journal
Nat Rev Cancer 4:381-93 (2004)
DOI:10.1038/nrc1364
Reference
  Authors
Linehan WM, Walther MM, Zbar B.
  Title
The genetic basis of cancer of the kidney.
  Journal
J Urol 170:2163-72 (2003)
DOI:10.1097/01.ju.0000096060.92397.ed
Reference
  Authors
Kim WY, Kaelin WG.
  Title
Role of VHL gene mutation in human cancer.
  Journal
J Clin Oncol 22:4991-5004 (2004)
DOI:10.1200/JCO.2004.05.061
Reference
  Authors
Sudarshan S, Linehan WM, Neckers L.
  Title
HIF and fumarate hydratase in renal cancer.
  Journal
Br J Cancer 96:403-7 (2007)
DOI:10.1038/sj.bjc.6603547
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)
DOI:10.1038/ncpuro0711
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)
DOI:10.1038/nrm1261
Reference
  Authors
Muller-Hocker J, Babaryka G, Schmid I, Jung A
  Title
Overexpression of cyclin D1, D3, and p21 in an infantile renal carcinoma with Xp11.2 TFE3-gene fusion.
  Journal
Pathol Res Pract 204:589-97 (2008)
DOI:10.1016/j.prp.2008.01.010
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)
DOI:10.1093/hmg/11.20.2489
Reference
  Authors
Kauffman EC, Ricketts CJ, Rais-Bahrami S, Yang Y, Merino MJ, Bottaro DP, Srinivasan R, Linehan WM
  Title
Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers.
  Journal
Nat Rev Urol 11:465-75 (2014)
DOI:10.1038/nrurol.2014.162
Reference
  Authors
Skalsky YM, Ajuh PM, Parker C, Lamond AI, Goodwin G, Cooper CS
  Title
PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors.
  Journal
Oncogene 20:178-87 (2001)
DOI:10.1038/sj.onc.1204056
Reference
  Authors
Medendorp K, van Groningen JJ, Vreede L, Hetterschijt L, Brugmans L, van den Hurk WH, van Kessel AG
  Title
The renal cell carcinoma-associated oncogenic fusion protein PRCCTFE3 provokes p21 WAF1/CIP1-mediated cell cycle delay.
  Journal
Exp Cell Res 315:2399-409 (2009)
DOI:10.1016/j.yexcr.2009.04.022
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