KEGG   PATHWAY: hsa05219Help
Entry
hsa05219                    Pathway                                

Name
Bladder cancer - Homo sapiens (human)
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; Cancers
BRITE hierarchy
Pathway map
Bladder cancer
hsa05219

All organismsOrtholog table
Disease
H00022  
Bladder cancer
Organism
Homo sapiens (human) [GN:hsa]
Gene
2261  
FGFR3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
369  
ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  
BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
9252  
RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
4609  
MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
11186  
RASSF1; Ras association domain family member 1 [KO:K09850]
1612  
DAPK1; death associated protein kinase 1 [KO:K08803] [EC:2.7.11.1]
1613  
DAPK3; death-associated protein kinase 3 [KO:K08803] [EC:2.7.11.1]
23604  
DAPK2; death-associated protein kinase 2 [KO:K08803] [EC:2.7.11.1]
1029  
CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
4193  
MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
7157  
TP53; tumor protein p53 [KO:K04451]
1026  
CDKN1A; cyclin-dependent kinase inhibitor 1A [KO:K06625]
595  
CCND1; cyclin D1 [KO:K04503]
1019  
CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
5925  
RB1; retinoblastoma 1 [KO:K06618]
1869  
E2F1; E2F transcription factor 1 [KO:K17454]
1870  
E2F2; E2F transcription factor 2 [KO:K09389]
1871  
E2F3; E2F transcription factor 3 [KO:K06620]
7057  
THBS1; thrombospondin 1 [KO:K16857]
1839  
HBEGF; heparin binding EGF like growth factor [KO:K08523]
4313  
MMP2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
4318  
MMP9; matrix metallopeptidase 9 [KO:K01403] [EC:3.4.24.35]
7380  
UPK3A; uroplakin 3A [KO:K19520]
6714  
SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
1950  
EGF; epidermal growth factor [KO:K04357]
2064  
ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
1956  
EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
1890  
TYMP; thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
7422  
VEGFA; vascular endothelial growth factor A [KO:K05448]
4312  
MMP1; matrix metallopeptidase 1 [KO:K01388] [EC:3.4.24.7]
3576  
CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
999  
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)
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)
Reference
  Authors
Wu XR.
  Title
Urothelial tumorigenesis: a tale of divergent pathways.
  Journal
Nat Rev Cancer 5:713-25 (2005)
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)
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)
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)
Reference
  Authors
Williams SG, Stein JP.
  Title
Molecular pathways in bladder cancer.
  Journal
Urol Res 32:373-85 (2004)
KO pathway
 

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