KEGG   PATHWAY: mpuf05219
Entry
mpuf05219                   Pathway                                
Name
Bladder cancer - Mustela putorius furo (domestic ferret)
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
mpuf05219  Bladder cancer
mpuf05219

Organism
Mustela putorius furo (domestic ferret) [GN:mpuf]
Gene
101691659  FGFR3; fibroblast growth factor receptor 3 isoform X10 [KO:K05094] [EC:2.7.10.1]
101681355  HRAS; GTPase HRas isoform X1 [KO:K02833]
101681333  KRAS; GTPase KRas isoform X3 [KO:K07827]
101683038  NRAS; GTPase NRas [KO:K07828]
101687799  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
101671970  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
101690482  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101680975  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101678743  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101679748  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101671073  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101690295  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
101689754  MYC; myc proto-oncogene protein isoform X3 [KO:K04377]
101683293  RASSF1; ras association domain-containing protein 1 [KO:K09850]
101679190  DAPK2; death-associated protein kinase 2 isoform X1 [KO:K08803] [EC:2.7.11.1]
101682361  DAPK1; death-associated protein kinase 1 isoform X1 [KO:K08803] [EC:2.7.11.1]
101676683  DAPK3; death-associated protein kinase 3 isoform X1 [KO:K08803] [EC:2.7.11.1]
101672555  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
101689782  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
101677794  TP53; cellular tumor antigen p53 [KO:K04451]
101671066  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101670844  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
101673063  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
101685420  RB1; retinoblastoma-associated protein [KO:K06618]
101681681  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
101678713  E2F2; transcription factor E2F2 [KO:K09389]
101693488  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
101694197  THBS1; thrombospondin-1 [KO:K16857]
101688241  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
101675156  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
101677351  MMP9; matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
101676575  UPK3A; uroplakin-3a [KO:K19520]
106003305  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101682951  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
101693248  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
101685824  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
101675945  VEGFA; vascular endothelial growth factor A [KO:K05448]
101688986  MMP1; interstitial collagenase [KO:K01388] [EC:3.4.24.7]
101689258  interstitial collagenase isoform X1 [KO:K01388] [EC:3.4.24.7]
101676365  CXCL8; interleukin-8 [KO:K10030]
101680359  cadherin-1-like isoform X1 [KO:K05689]
101682346  CDH1; cadherin-1 [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
mpuf04010  MAPK signaling pathway
mpuf04012  ErbB signaling pathway
mpuf04110  Cell cycle
mpuf04115  p53 signaling pathway
mpuf04370  VEGF signaling pathway
mpuf04520  Adherens junction
KO pathway
ko05219   
LinkDB

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