KEGG   PATHWAY: elk05219
Entry
elk05219                    Pathway                                
Name
Bladder cancer - Enhydra lutris kenyoni (northern sea otter)
Description
The urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carcinoma are bladder carcinomas, and urothelial carcinomas of the renal pelvis and ureter account for only approximately 7% of the total. Urothelial tumours arise and evolve through divergent phenotypic pathways. Some tumours progress from urothelial hyperplasia to low-grade non-invasive superficial papillary tumours. More aggressive variants arise either from flat, high-grade carcinoma in situ (CIS) and progress to invasive tumours, or they arise de novo as invasive tumours. Low-grade papillary tumors frequently show a constitutive activation of the receptor tyrosine kinase-Ras pathway, exhibiting activating mutations in the HRAS and fibroblast growth factor receptor 3 (FGFR3) genes. In contrast, CIS and invasive tumors frequently show alterations in the TP53 and RB genes and pathways. Invasion and metastases are promoted by several factors that alter the tumour microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF).
Class
Human Diseases; Cancer: specific types
Pathway map
elk05219  Bladder cancer
elk05219

Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111149137  fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
111140316  GTPase HRas isoform X1 [KO:K02833]
111159984  GTPase KRas isoform X1 [KO:K07827]
111143238  GTPase NRas [KO:K07828]
111150582  serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
111151941  serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
111144322  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111153158  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111161815  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111162236  LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111142759  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111148567  ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
111146783  myc proto-oncogene protein [KO:K04377]
111143767  ras association domain-containing protein 1 isoform X1 [KO:K09850]
111161839  death-associated protein kinase 3 [KO:K08803] [EC:2.7.11.1]
111153261  death-associated protein kinase 2 isoform X1 [KO:K08803] [EC:2.7.11.1]
111153491  death-associated protein kinase 1 isoform X1 [KO:K08803] [EC:2.7.11.1]
111159871  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
111142120  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
111161133  cellular tumor antigen p53 [KO:K04451]
111147618  cyclin-dependent kinase inhibitor 1 [KO:K06625]
111149458  G1/S-specific cyclin-D1 [KO:K04503]
111160230  cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
111146911  retinoblastoma-associated protein [KO:K06618]
111141556  transcription factor E2F1 [KO:K17454]
111154729  transcription factor E2F2 isoform X1 [KO:K09389]
111138625  transcription factor E2F3 isoform X1 [KO:K06620]
111161597  thrombospondin-1 [KO:K16857]
111141144  proheparin-binding EGF-like growth factor [KO:K08523]
111157340  72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
111141396  matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
111157691  uroplakin-3a isoform X1 [KO:K19520]
111141563  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
111156359  pro-epidermal growth factor isoform X1 [KO:K04357]
111151268  receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
111157042  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111147726  vascular endothelial growth factor A [KO:K05448]
111153766  interstitial collagenase [KO:K01388] [EC:3.4.24.7]
111153845  interstitial collagenase-like [KO:K01388] [EC:3.4.24.7]
111149115  interleukin-8 [KO:K10030]
111152800  LOW QUALITY PROTEIN: cadherin-1-like [KO:K05689]
111152817  cadherin-1 isoform X1 [KO:K05689]
Reference
  Authors
Mitra AP, Datar RH, Cote RJ.
  Title
Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification.
  Journal
J Clin Oncol 24:5552-64 (2006)
DOI:10.1200/JCO.2006.08.2073
Reference
  Authors
Wolff EM, Liang G, Jones PA.
  Title
Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer.
  Journal
Nat Clin Pract Urol 2:502-10 (2005)
DOI:10.1038/ncpuro0318
Reference
  Authors
Wu XR.
  Title
Urothelial tumorigenesis: a tale of divergent pathways.
  Journal
Nat Rev Cancer 5:713-25 (2005)
DOI:10.1038/nrc1697
Reference
  Authors
Brown NS, Jones A, Fujiyama C, Harris AL, Bicknell R.
  Title
Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors.
  Journal
Cancer Res 60:6298-302 (2000)
Reference
  Authors
Bellmunt J, Hussain M, Dinney CP.
  Title
Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family.
  Journal
Crit Rev Oncol Hematol 46 Suppl:S85-104 (2003)
DOI:10.1016/S1040-8428(03)00067-2
Reference
  Authors
Sugano K, Kakizoe T.
  Title
Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging.
  Journal
Nat Clin Pract Urol 3:642-52 (2006)
DOI:10.1038/ncpuro0649
Reference
  Authors
Dunn KL, Espino PS, Drobic B, He S, Davie JR.
  Title
The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling.
  Journal
Biochem Cell Biol 83:1-14 (2005)
DOI:10.1139/o04-121
Reference
  Authors
Williams SG, Stein JP.
  Title
Molecular pathways in bladder cancer.
  Journal
Urol Res 32:373-85 (2004)
DOI:10.1007/s00240-003-0345-y
Related
pathway
elk04010  MAPK signaling pathway
elk04012  ErbB signaling pathway
elk04110  Cell cycle
elk04115  p53 signaling pathway
elk04370  VEGF signaling pathway
elk04520  Adherens junction
KO pathway
ko05219   
LinkDB

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