KEGG   PATHWAY: mmyo05219
Entry
mmyo05219                   Pathway                                
Name
Bladder cancer - Myotis myotis (greater mouse-eared 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
mmyo05219  Bladder cancer
mmyo05219

Organism
Myotis myotis (greater mouse-eared bat) [GN:mmyo]
Gene
118665364  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
118648965  HRAS; GTPase HRas isoform X1 [KO:K02833]
118649554  KRAS; GTPase KRas isoform X1 [KO:K07827]
118672986  NRAS; GTPase NRas [KO:K07828]
118653778  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
118666337  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
118668076  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
118654213  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
118657986  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
118678650  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
118656605  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
118659250  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
118670599  MYC; myc proto-oncogene protein [KO:K04377]
118668448  RASSF1; LOW QUALITY PROTEIN: ras association domain-containing protein 1 [KO:K09850]
118658400  DAPK3; death-associated protein kinase 3 [KO:K08803] [EC:2.7.11.1]
118667408  death-associated protein kinase 1 isoform X1 [KO:K08803] [EC:2.7.11.1]
118653501  DAPK2; death-associated protein kinase 2 isoform X1 [KO:K08803] [EC:2.7.11.1]
118667589  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
118650326  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
118672084  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
118659964  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
118665181  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
118651037  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
118651068  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
118663841  E2F1; transcription factor E2F1 [KO:K17454]
118676426  E2F2; transcription factor E2F2 [KO:K09389]
118676306  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
118649603  THBS1; thrombospondin-1 [KO:K16857]
118658125  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
118654551  proheparin-binding EGF-like growth factor [KO:K08523]
118674505  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
118663534  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
118652156  UPK3A; uroplakin-3a [KO:K19520]
118662917  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
118672981  EGF; pro-epidermal growth factor [KO:K04357]
118671218  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
118665909  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
118657380  thymidine phosphorylase [KO:K00758] [EC:2.4.2.4]
118660010  VEGFA; vascular endothelial growth factor A [KO:K05448]
118664460  MMP1; interstitial collagenase [KO:K01388] [EC:3.4.24.7]
118670543  CXCL8; interleukin-8 [KO:K10030]
118671044  C-X-C motif chemokine 15-like [KO:K10030]
118674502  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
mmyo04010  MAPK signaling pathway
mmyo04012  ErbB signaling pathway
mmyo04110  Cell cycle
mmyo04115  p53 signaling pathway
mmyo04370  VEGF signaling pathway
mmyo04520  Adherens junction
KO pathway
ko05219   
LinkDB

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