KEGG   PATHWAY: pale05219
Entry
pale05219                   Pathway                                
Name
Bladder cancer - Pteropus alecto (black flying fox)
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
pale05219  Bladder cancer
pale05219

Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102878342  FGFR3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
102896270  HRAS; GTPase HRas isoform X3 [KO:K02833]
102895590  KRAS; GTPase KRas isoform X1 [KO:K07827]
102885950  NRAS; GTPase NRas isoform X2 [KO:K07828]
102877877  ARAF; serine/threonine-protein kinase A-Raf isoform X2 [KO:K08845] [EC:2.7.11.1]
102878393  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102897122  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102879034  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102895390  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102885749  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102897813  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
102895524  MYC; myc proto-oncogene protein [KO:K04377]
102879898  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
102892714  DAPK3; death-associated protein kinase 3 [KO:K08803] [EC:2.7.11.1]
102885201  DAPK2; death-associated protein kinase 2 isoform X2 [KO:K08803] [EC:2.7.11.1]
102891860  DAPK1; death-associated protein kinase 1 [KO:K08803] [EC:2.7.11.1]
102896422  LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 2A [KO:K06621]
102884281  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
102889604  TP53; cellular tumor antigen p53 [KO:K04451]
102894049  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102885330  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102894222  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102893019  RB1; retinoblastoma-associated protein [KO:K06618]
102895276  E2F1; transcription factor E2F1 [KO:K17454]
102884459  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
102887239  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102898784  THBS1; thrombospondin-1 [KO:K16857]
102882842  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
102883808  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
102889517  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
102879181  UPK3A; uroplakin-3a isoform X1 [KO:K19520]
102891249  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
102891552  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102885300  ERBB2; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
102893495  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102880526  TYMP; LOW QUALITY PROTEIN: thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
102890394  VEGFA; vascular endothelial growth factor A isoform X2 [KO:K05448]
102893881  MMP1; interstitial collagenase [KO:K01388] [EC:3.4.24.7]
102892534  CXCL8; interleukin-8 [KO:K10030]
102886394  CDH1; cadherin-1 isoform X1 [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
pale04010  MAPK signaling pathway
pale04012  ErbB signaling pathway
pale04110  Cell cycle
pale04115  p53 signaling pathway
pale04370  VEGF signaling pathway
pale04520  Adherens junction
KO pathway
ko05219   
LinkDB

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