KEGG   PATHWAY: mmur05219
Entry
mmur05219                   Pathway                                
Name
Bladder cancer - Microcebus murinus (gray mouse lemur)
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
mmur05219  Bladder cancer
mmur05219

Organism
Microcebus murinus (gray mouse lemur) [GN:mmur]
Gene
105856032  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
105874032  HRAS; GTPase HRas [KO:K02833]
105857286  KRAS; GTPase KRas isoform X1 [KO:K07827]
105878710  NRAS; GTPase NRas [KO:K07828]
105862190  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
105873244  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
105882676  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105868083  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105873938  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105870697  mitogen-activated protein kinase 6-like [KO:K04371] [EC:2.7.11.24]
105877796  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105871124  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105876284  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
105882748  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
105875006  RASSF1; ras association domain-containing protein 1 isoform X3 [KO:K09850]
105873943  DAPK3; death-associated protein kinase 3 [KO:K08803] [EC:2.7.11.1]
105868109  DAPK2; death-associated protein kinase 2 isoform X1 [KO:K08803] [EC:2.7.11.1]
105855614  DAPK1; death-associated protein kinase 1 [KO:K08803] [EC:2.7.11.1]
105874194  cyclin-dependent kinase inhibitor 2A [KO:K06621]
105884627  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
105877486  TP53; cellular tumor antigen p53 [KO:K04451]
105861439  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105867511  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
105877995  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
105855966  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
105866012  E2F1; transcription factor E2F1 [KO:K17454]
105863547  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105865199  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105872421  THBS1; thrombospondin-1 [KO:K16857]
105862636  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
105866549  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
105859286  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105867630  UPK3A; uroplakin-3a [KO:K19520]
105866030  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
105872305  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
105872099  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
105877217  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
105885000  TYMP; thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
105875869  VEGFA; vascular endothelial growth factor A [KO:K05448]
105874564  MMP1; interstitial collagenase [KO:K01388] [EC:3.4.24.7]
105874586  interstitial collagenase-like [KO:K01388] [EC:3.4.24.7]
105871610  interstitial collagenase-like [KO:K01388] [EC:3.4.24.7]
105860250  CXCL8; interleukin-8 [KO:K10030]
105858954  CDH1; LOW QUALITY PROTEIN: 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
mmur04010  MAPK signaling pathway
mmur04012  ErbB signaling pathway
mmur04110  Cell cycle
mmur04115  p53 signaling pathway
mmur04370  VEGF signaling pathway
mmur04520  Adherens junction
KO pathway
ko05219   
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