KEGG   PATHWAY: lav05219
lav05219                    Pathway                                

Bladder cancer - Loxodonta africana (African savanna elephant)
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
lav05219  Bladder cancer

Loxodonta africana (African savanna elephant) [GN:lav]
100674054  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:]
100661512  KRAS; GTPase KRas isoform X2 [KO:K07827]
100659051  NRAS; GTPase NRas [KO:K07828]
100671404  ARAF; serine/threonine-protein kinase A-Raf isoform X3 [KO:K08845] [EC:]
100664119  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:]
100655727  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
100667623  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
100657587  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
100658240  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
100665157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
100664075  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:]
100665874  MYC; myc proto-oncogene protein [KO:K04377]
100668441  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
100669366  DAPK1; death-associated protein kinase 1 isoform X2 [KO:K08803] [EC:]
100670001  DAPK3; death-associated protein kinase 3 isoform X2 [KO:K08803] [EC:]
100669221  DAPK2; death-associated protein kinase 2 isoform X1 [KO:K08803] [EC:]
104845647  cyclin-dependent kinase inhibitor 2A-like [KO:K06621]
100669448  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X2 [KO:K06643] [EC:]
100663725  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
100671706  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100669703  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104847103  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:]
100673196  RB1; retinoblastoma-associated protein [KO:K06618]
100664468  E2F1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
100665816  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
100656140  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100667431  THBS1; thrombospondin-1 [KO:K16857]
100675899  HBEGF; proheparin-binding EGF-like growth factor isoform X2 [KO:K08523]
100659450  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:]
100664260  MMP9; LOW QUALITY PROTEIN: matrix metalloproteinase-9 [KO:K01403] [EC:]
100658957  uroplakin-3a-like [KO:K19520]
100659478  UPK3A; uroplakin-3a [KO:K19520]
100675475  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:]
100670137  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
100662583  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X2 [KO:K05083] [EC:]
100659125  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:]
100656090  TYMP; thymidine phosphorylase [KO:K00758] [EC:]
100661392  VEGFA; vascular endothelial growth factor A [KO:K05448]
100656422  MMP1; interstitial collagenase [KO:K01388] [EC:]
100664099  CXCL8; interleukin-8 [KO:K10030]
100659456  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)
lav04010  MAPK signaling pathway
lav04012  ErbB signaling pathway
lav04110  Cell cycle
lav04115  p53 signaling pathway
lav04370  VEGF signaling pathway
lav04520  Adherens junction
KO pathway

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