KEGG   PATHWAY: morg05211
Entry
morg05211                   Pathway                                
Name
Renal cell carcinoma - Microtus oregoni (creeping vole)
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
morg05211  Renal cell carcinoma
morg05211

Organism
Microtus oregoni (creeping vole) [GN:morg]
Gene
121452243  Hif1a; hypoxia-inducible factor 1-alpha isoform X1 [KO:K08268]
121432866  Epas1; endothelial PAS domain-containing protein 1 [KO:K09095]
121452582  Egln3; LOW QUALITY PROTEIN: prolyl hydroxylase EGLN3 [KO:K09592] [EC:1.14.11.29]
121446970  Egln1; egl nine homolog 1 isoform X1 [KO:K09592] [EC:1.14.11.29]
121449369  Egln2; prolyl hydroxylase EGLN2 isoform X1 [KO:K09592] [EC:1.14.11.29]
121441314  Vhl; von Hippel-Lindau disease tumor suppressor [KO:K03871]
121462395  elongin-C-like [KO:K03872]
121458568  Eloc; elongin-C [KO:K03872]
121432494  elongin-C-like [KO:K03872]
121455609  elongin-B-like [KO:K03873]
121463606  Elob; elongin-B [KO:K03873]
121465562  elongin-B-like [KO:K03873]
121453567  elongin-B-like [KO:K03873]
121443682  elongin-B-like [KO:K03873]
121443704  elongin-B-like [KO:K03873]
121443712  elongin-B-like [KO:K03873]
121443714  elongin-B-like [KO:K03873]
121448873  elongin-B-like [KO:K03873]
121448875  elongin-B-like [KO:K03873]
121448876  elongin-B-like [KO:K03873]
121448877  elongin-B-like [KO:K03873]
121448878  elongin-B-like [KO:K03873]
121448879  elongin-B-like [KO:K03873]
121448880  elongin-B-like [KO:K03873]
121448881  elongin-B-like [KO:K03873]
121448883  elongin-B-like [KO:K03873]
121461000  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
121444018  E3 ubiquitin-protein ligase RBX1-like [KO:K03868] [EC:2.3.2.32]
121440750  Cul2; cullin-2 [KO:K03870]
121450566  aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097]
121437877  aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097]
121447117  Arnt2; aryl hydrocarbon receptor nuclear translocator 2 isoform X1 [KO:K15589]
121461086  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
121463856  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
121448106  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
121450557  Vegfa; vascular endothelial growth factor A isoform X1 [KO:K05448]
121449432  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
121435842  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
121452547  Tgfb3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
121461545  Pdgfb; platelet-derived growth factor subunit B [KO:K17386]
121435991  Tgfa; LOW QUALITY PROTEIN: protransforming growth factor alpha [KO:K08774]
121459077  hepatocyte growth factor-like isoform X1 [KO:K05460]
121434777  hepatocyte growth factor isoform X1 [KO:K05460]
121463319  Met; hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
121455737  Gab1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
121464321  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121453059  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
121448116  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
121441780  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like [KO:K00922] [EC:2.7.1.153]
121455952  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
121462841  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
121448002  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
121434429  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
121449224  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121435875  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
121454562  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
121456193  Crk; adapter molecule crk isoform X1 [KO:K04438]
121464797  Crkl; crk-like protein [KO:K04438]
121462617  Rapgef1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
121437958  ras-related protein Rap-1A [KO:K04353]
121449757  ras-related protein Rap-1A [KO:K04353]
121461538  Rap1b; ras-related protein Rap-1b [KO:K07836]
121444074  LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
121445401  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
121445448  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
121445466  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
121445498  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
121445512  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
121445529  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
121445850  Ptpn11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
121446943  LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
121463365  growth factor receptor-bound protein 2-like [KO:K04364]
121436142  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
121452307  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
121432861  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
121458090  Hras; GTPase HRas [KO:K02833]
121466497  Kras; GTPase KRas isoform X1 [KO:K07827]
121437938  Nras; GTPase NRas [KO:K07828]
121463309  serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
121435346  serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
121443425  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
121466018  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
121459389  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
121458143  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121464725  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121451646  Ets1; protein C-ets-1 isoform X1 [KO:K02678]
121448148  Jun; transcription factor AP-1 [KO:K04448]
121464919  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
121448012  Cdc42; cell division control protein 42 homolog isoform X1 [KO:K04393]
121458901  serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
121447291  serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
121461945  Pak2; serine/threonine-protein kinase PAK 2 [KO:K04410] [EC:2.7.11.1]
121444017  Pak3; serine/threonine-protein kinase PAK 3 isoform X1 [KO:K05733] [EC:2.7.11.1]
121439805  serine/threonine-protein kinase PAK 3-like [KO:K05733] [EC:2.7.11.1]
121450019  Pak4; serine/threonine-protein kinase PAK 4 [KO:K05734] [EC:2.7.11.1]
121460477  Pak5; serine/threonine-protein kinase PAK 5 isoform X1 [KO:K05736] [EC:2.7.11.1]
121465803  serine/threonine-protein kinase PAK 6 [KO:K05735] [EC:2.7.11.1]
121451042  Prcc; proline-rich protein PRCC [KO:K13105]
121442603  transcription factor E3 isoform X1 [KO:K09105]
121442681  transcription factor E3-like [KO:K09105]
121435589  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
121435777  Fh; fumarate hydratase, mitochondrial [KO:K01679] [EC:4.2.1.2]
121457113  Flcn; folliculin [KO:K09594]
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)
DOI:10.1056/NEJMra043172
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)
DOI:10.1038/nrc1364
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)
DOI:10.1097/01.ju.0000096060.92397.ed
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)
DOI:10.1200/JCO.2004.05.061
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)
DOI:10.1038/sj.bjc.6603547
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)
DOI:10.1038/ncpuro0711
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)
DOI:10.1038/nrm1261
Reference
PMID:18358634
  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
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)
DOI:10.1093/hmg/11.20.2489
Reference
PMID:25048860
  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
PMID:11313942
  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
PMID:19422821
  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
morg00020  Citrate cycle (TCA cycle)
morg04010  MAPK signaling pathway
morg04066  HIF-1 signaling pathway
morg04120  Ubiquitin mediated proteolysis
morg04350  TGF-beta signaling pathway
morg04370  VEGF signaling pathway
KO pathway
ko05211   
LinkDB

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