KEGG   PATHWAY: ngi05219
ngi05219                    Pathway                                

Bladder cancer - Nannospalax galili (Upper Galilee mountains blind mole rat)
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
ngi05219  Bladder cancer

Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]
103741127  Fgfr3; fibroblast growth factor receptor 3 [KO:K05094] [EC:]
103751075  Hras; HRas proto-oncogene, GTPase [KO:K02833]
103736717  Kras; KRAS proto-oncogene, GTPase [KO:K07827]
103734938  Nras; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103741627  Araf; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:]
103726107  Braf; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:]
103751450  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:]
103736801  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
103737276  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
103741442  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
103726390  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
103724612  Rps6ka5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:]
103743920  Myc; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
103750153  Rassf1; Ras association domain family member 1 [KO:K09850]
103737271  Dapk3; death associated protein kinase 3 [KO:K08803] [EC:]
103734199  Dapk1; death associated protein kinase 1 [KO:K08803] [EC:]
103750086  Dapk2; death associated protein kinase 2 [KO:K08803] [EC:]
103730663  cyclin-dependent kinase 4 inhibitor B-like [KO:K06621]
103745079  Mdm2; MDM2 proto-oncogene [KO:K06643] [EC:]
103752115  Tp53; tumor protein p53 [KO:K04451]
103739652  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
103751498  Ccnd1; cyclin D1 [KO:K04503]
103742900  Cdk4; cyclin dependent kinase 4 [KO:K02089] [EC:]
103726779  Rb1; RB transcriptional corepressor 1 [KO:K06618]
103751571  E2f1; E2F transcription factor 1 [KO:K17454]
103746411  E2f2; E2F transcription factor 2 [KO:K09389]
103745641  E2f3; E2F transcription factor 3 [KO:K06620]
103727450  Thbs1; thrombospondin 1 [KO:K16857]
103743072  Hbegf; heparin binding EGF like growth factor [KO:K08523]
103731682  Mmp2; matrix metallopeptidase 2 [KO:K01398] [EC:]
103751232  Mmp9; matrix metallopeptidase 9 [KO:K01403] [EC:]
103743422  Upk3a; uroplakin 3A [KO:K19520]
103752029  Src; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:]
103742642  Egf; epidermal growth factor [KO:K04357]
103743825  Erbb2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:]
103748852  epidermal growth factor receptor [KO:K04361] [EC:]
103735486  Tymp; thymidine phosphorylase [KO:K00758] [EC:]
103730772  Vegfa; vascular endothelial growth factor A [KO:K05448]
103731579  interstitial collagenase A-like [KO:K01388] [EC:]
103731678  interstitial collagenase-like [KO:K01388] [EC:]
103742429  Cxcl8; C-X-C motif chemokine ligand 8 [KO:K10030]
103734864  Cdh1; cadherin 1 [KO:K05689]
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)
ngi04010  MAPK signaling pathway
ngi04012  ErbB signaling pathway
ngi04110  Cell cycle
ngi04115  p53 signaling pathway
ngi04370  VEGF signaling pathway
ngi04520  Adherens junction
KO pathway

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