KEGG   PATHWAY: ko05219
ko05219                     Pathway                                
Bladder cancer
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).
Human Diseases; Cancer: specific types
Pathway map
ko05219  Bladder cancer

H00022  Bladder cancer
K05094  fibroblast growth factor receptor 3 [EC:]
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K08845  A-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04369  mitogen-activated protein kinase kinase 2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K04445  ribosomal protein S6 kinase alpha-5 [EC:]
K04377  Myc proto-oncogene protein
K09850  Ras association domain-containing protein 1
K08803  death-associated protein kinase [EC:]
K06621  cyclin-dependent kinase inhibitor 2A
K06643  E3 ubiquitin-protein ligase Mdm2 [EC:]
K04451  tumor protein p53
K06625  cyclin-dependent kinase inhibitor 1A
K04503  G1/S-specific cyclin-D1
K02089  cyclin-dependent kinase 4 [EC:]
K06618  retinoblastoma-associated protein
K17454  transcription factor E2F1
K09389  transcription factor E2F2
K06620  transcription factor E2F3
K16857  thrombospondin 1
K08523  heparin-binding EGF-like growth factor
K01398  matrix metalloproteinase-2 (gelatinase A) [EC:]
K01403  matrix metalloproteinase-9 (gelatinase B) [EC:]
K19520  uroplakin-3a
K05704  tyrosine-protein kinase Src [EC:]
K04357  epidermal growth factor
K05083  receptor tyrosine-protein kinase erbB-2 [EC:]
K04361  epidermal growth factor receptor [EC:]
K00758  thymidine phosphorylase [EC:]
K05448  vascular endothelial growth factor A
K01388  matrix metalloproteinase-1 (interstitial collagenase) [EC:]
K10030  interleukin 8
K05689  cadherin 1, type 1, E-cadherin
Mitra AP, Datar RH, Cote RJ.
Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification.
J Clin Oncol 24:5552-64 (2006)
Wolff EM, Liang G, Jones PA.
Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer.
Nat Clin Pract Urol 2:502-10 (2005)
Wu XR.
Urothelial tumorigenesis: a tale of divergent pathways.
Nat Rev Cancer 5:713-25 (2005)
Brown NS, Jones A, Fujiyama C, Harris AL, Bicknell R.
Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors.
Cancer Res 60:6298-302 (2000)
Bellmunt J, Hussain M, Dinney CP.
Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family.
Crit Rev Oncol Hematol 46 Suppl:S85-104 (2003)
Sugano K, Kakizoe T.
Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging.
Nat Clin Pract Urol 3:642-52 (2006)
Dunn KL, Espino PS, Drobic B, He S, Davie JR.
The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling.
Biochem Cell Biol 83:1-14 (2005)
Williams SG, Stein JP.
Molecular pathways in bladder cancer.
Urol Res 32:373-85 (2004)
ko04010  MAPK signaling pathway
ko04012  ErbB signaling pathway
ko04110  Cell cycle
ko04115  p53 signaling pathway
ko04370  VEGF signaling pathway
ko04520  Adherens junction

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