KEGG   PATHWAY: csab05219
Entry
csab05219                   Pathway                                
Name
Bladder cancer - Chlorocebus sabaeus (green monkey)
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
csab05219  Bladder cancer
csab05219

Organism
Chlorocebus sabaeus (green monkey) [GN:csab]
Gene
103246479  FGFR3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
103246363  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103218763  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103224167  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103231895  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
103227022  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103228031  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103245451  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103233717  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103222941  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103230532  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103229550  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
103237430  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
103227676  RASSF1; Ras association domain family member 1 [KO:K09850]
103233720  DAPK3; death associated protein kinase 3 [KO:K08803] [EC:2.7.11.1]
103219698  DAPK1; death associated protein kinase 1 [KO:K08803] [EC:2.7.11.1]
103245501  death-associated protein kinase 3-like [KO:K08803] [EC:2.7.11.1]
103245502  DAPK2; death associated protein kinase 2 [KO:K08803] [EC:2.7.11.1]
103219354  cyclin-dependent kinase inhibitor 2A, isoform 4 [KO:K06621]
103238687  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
103242323  TP53; tumor protein p53 [KO:K04451]
103221583  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
103246489  CCND1; cyclin D1 [KO:K04503]
103238589  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103214406  RB1; RB transcriptional corepressor 1 [KO:K06618]
103248605  E2F1; E2F transcription factor 1 [KO:K17454]
103225395  E2F2; E2F transcription factor 2 [KO:K09389]
103222084  E2F3; E2F transcription factor 3 [KO:K06620]
103245860  THBS1; thrombospondin 1 [KO:K16857]
103244654  HBEGF; heparin binding EGF like growth factor [KO:K08523]
103233007  MMP2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
103245064  MMP9; matrix metallopeptidase 9 [KO:K01403] [EC:3.4.24.35]
103223470  UPK3A; uroplakin 3A [KO:K19520]
103246384  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
103236114  EGF; epidermal growth factor [KO:K04357]
103243533  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
103226055  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103223569  TYMP; thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
103221446  VEGFA; vascular endothelial growth factor A [KO:K05448]
103248335  MMP1; matrix metallopeptidase 1 [KO:K01388] [EC:3.4.24.7]
103235786  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
103233229  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
csab04010  MAPK signaling pathway
csab04012  ErbB signaling pathway
csab04110  Cell cycle
csab04115  p53 signaling pathway
csab04370  VEGF signaling pathway
csab04520  Adherens junction
KO pathway
ko05219   
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