KEGG   PATHWAY: pdic05219
Entry
pdic05219                   Pathway                                
Name
Bladder cancer - Phyllostomus discolor (pale spear-nosed bat)
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
pdic05219  Bladder cancer
pdic05219

Organism
Phyllostomus discolor (pale spear-nosed bat) [GN:pdic]
Gene
114489924  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
114499504  HRAS; GTPase HRas isoform X2 [KO:K02833]
114512682  KRAS; GTPase KRas isoform X1 [KO:K07827]
114489186  NRAS; GTPase NRas [KO:K07828]
114504860  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
114507230  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
114501905  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
114491735  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
114503388  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114510156  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114496946  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114493110  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
114514698  MYC; myc proto-oncogene protein [KO:K04377]
114501425  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
114503216  DAPK3; death-associated protein kinase 3 [KO:K08803] [EC:2.7.11.1]
114493369  DAPK2; death-associated protein kinase 2 isoform X3 [KO:K08803] [EC:2.7.11.1]
114493387  DAPK1; death-associated protein kinase 1 isoform X1 [KO:K08803] [EC:2.7.11.1]
114513642  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
114515376  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
114494317  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
114500683  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
114512697  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
114508470  RB1; LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618]
114506109  E2F1; transcription factor E2F1 [KO:K17454]
114496714  E2F2; transcription factor E2F2 [KO:K09389]
114496340  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
114491731  THBS1; thrombospondin-1 isoform X1 [KO:K16857]
114509723  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
114488295  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
114506744  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
114513951  UPK3A; uroplakin-3a [KO:K19520]
114506489  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
114492590  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
114502459  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
114507607  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
114513964  LOW QUALITY PROTEIN: thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
114494974  VEGFA; vascular endothelial growth factor A [KO:K05448]
114499949  MMP1; interstitial collagenase [KO:K01388] [EC:3.4.24.7]
118499766  C-X-C motif chemokine 15-like isoform X1 [KO:K10030]
114493304  CXCL8; interleukin-8 [KO:K10030]
114488249  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
pdic04010  MAPK signaling pathway
pdic04012  ErbB signaling pathway
pdic04110  Cell cycle
pdic04115  p53 signaling pathway
pdic04370  VEGF signaling pathway
pdic04520  Adherens junction
KO pathway
ko05219   
LinkDB

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