KEGG   PATHWAY: sbq05211
Entry
sbq05211                    Pathway                                

Name
Renal cell carcinoma - Saimiri boliviensis boliviensis (Bolivian squirrel monkey)
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; Cancer: specific types
Pathway map
sbq05211  Renal cell carcinoma
sbq05211

Organism
Saimiri boliviensis boliviensis (Bolivian squirrel monkey) [GN:sbq]
Gene
101044689  HIF1A; hypoxia-inducible factor 1-alpha isoform X2 [KO:K08268]
101052563  EPAS1; endothelial PAS domain-containing protein 1 [KO:K09095]
101051675  EGLN1; egl nine homolog 1 [KO:K09592] [EC:1.14.11.29]
101029000  EGLN3; egl nine homolog 3 [KO:K09592] [EC:1.14.11.29]
101045149  EGLN2; egl nine homolog 2 [KO:K09592] [EC:1.14.11.29]
104651216  VHL; LOW QUALITY PROTEIN: von Hippel-Lindau disease tumor suppressor [KO:K03871]
101050065  TCEB1; transcription elongation factor B polypeptide 1 isoform X1 [KO:K03872]
101037906  TCEB2; transcription elongation factor B polypeptide 2 [KO:K03873]
101031320  transcription elongation factor B polypeptide 2 [KO:K03873]
101050933  uncharacterized protein LOC101050933 [KO:K03873]
101031903  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101051445  CUL2; cullin-2 [KO:K03870]
101038733  ARNT; aryl hydrocarbon receptor nuclear translocator [KO:K09097]
101033734  ARNT2; aryl hydrocarbon receptor nuclear translocator 2 isoform X2 [KO:K15589]
101033803  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101050224  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101049410  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
101032691  VEGFA; vascular endothelial growth factor A isoform X1 [KO:K05448]
101047980  TGFB1; transforming growth factor beta-1 isoform X2 [KO:K13375]
101044624  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
101048819  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
101043776  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
101045311  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
101045517  HGF; hepatocyte growth factor isoform X1 [KO:K05460]
101038696  MET; hepatocyte growth factor receptor isoform X2 [KO:K05099] [EC:2.7.10.1]
101040995  GAB1; GRB2-associated-binding protein 1 isoform X4 [KO:K09593]
101029768  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101052779  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101027982  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101032496  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101033359  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101050592  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101034861  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101045714  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101040766  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101049631  BAD; bcl2-associated agonist of cell death [KO:K02158]
101051048  CRKL; crk-like protein [KO:K04438]
101029260  CRK; adapter molecule crk [KO:K04438]
101052399  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
101048450  RAP1A; ras-related protein Rap-1A [KO:K04353]
101036065  RAP1B; ras-related protein Rap-1b [KO:K07836]
101031381  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
101033019  LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
101038666  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101036943  SOS1; son of sevenless homolog 1 [KO:K03099]
101046427  SOS2; son of sevenless homolog 2 [KO:K03099]
101047663  HRAS; GTPase HRas isoform X2 [KO:K02833]
101047035  KRAS; GTPase KRas isoform X1 [KO:K07827]
101036877  NRAS; GTPase NRas [KO:K07828]
101043605  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101052142  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
101054052  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101040361  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101036151  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101038546  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101043202  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101036161  ETS1; protein C-ets-1 [KO:K02678]
101043809  JUN; transcription factor AP-1 [KO:K04448]
101042808  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
101050895  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
101042666  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
101035351  PAK2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
101030350  PAK3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
101030928  PAK4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
101045496  PAK7; serine/threonine-protein kinase PAK 7 [KO:K05736] [EC:2.7.11.1]
101053141  PAK6; serine/threonine-protein kinase PAK 6 isoform X1 [KO:K05735] [EC:2.7.11.1]
101036353  PRCC; proline-rich protein PRCC [KO:K13105]
101030478  TFE3; transcription factor E3 isoform X1 [KO:K09105]
101041919  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
101048662  FH; fumarate hydratase, mitochondrial [KO:K01679] [EC:4.2.1.2]
101050343  FLCN; folliculin isoform X1 [KO:K09594]
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)
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
Related
pathway
sbq00020  Citrate cycle (TCA cycle)
sbq04010  MAPK signaling pathway
sbq04066  HIF-1 signaling pathway
sbq04120  Ubiquitin mediated proteolysis
sbq04350  TGF-beta signaling pathway
sbq04370  VEGF signaling pathway
KO pathway
ko05211   
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