KEGG   PATHWAY: cfr05219
cfr05219                    Pathway                                

Bladder cancer - Camelus ferus (Wild Bactrian camel)
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
cfr05219  Bladder cancer

Camelus ferus (Wild Bactrian camel) [GN:cfr]
102512878  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:]
102524334  HRAS; GTPase HRas isoform X1 [KO:K02833]
102516372  KRAS; GTPase KRas isoform X1 [KO:K07827]
102509562  NRAS; GTPase NRas [KO:K07828]
102506774  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:]
102524100  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:]
102517521  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
102515937  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
102511209  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:]
102517586  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
102521659  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
102512204  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:]
102511086  MYC; myc proto-oncogene protein [KO:K04377]
102520308  RASSF1; ras association domain-containing protein 1 isoform X1 [KO:K09850]
102506911  DAPK2; death-associated protein kinase 2 isoform X2 [KO:K08803] [EC:]
102510747  DAPK3; death-associated protein kinase 3 [KO:K08803] [EC:]
102512779  DAPK1; LOW QUALITY PROTEIN: death-associated protein kinase 1 [KO:K08803] [EC:]
102522420  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:]
102524476  TP53; cellular tumor antigen p53 [KO:K04451]
102509404  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
102518309  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102522300  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:]
102516870  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
102517851  E2F1; transcription factor E2F1 [KO:K17454]
102515523  E2F2; transcription factor E2F2 [KO:K09389]
102513737  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102519986  THBS1; thrombospondin-1 [KO:K16857]
102510168  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
102521167  MMP2; 72 kDa type IV collagenase isoform X1 [KO:K01398] [EC:]
102509767  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:]
102515728  UPK3A; uroplakin-3a [KO:K19520]
102520048  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:]
102523769  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102519604  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:]
102504272  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:]
102514843  VEGFA; vascular endothelial growth factor A [KO:K05448]
102517049  MMP1; interstitial collagenase [KO:K01388] [EC:]
102506409  CXCL8; interleukin-8 [KO:K10030]
102518832  cadherin-1 isoform X2 [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)
cfr04010  MAPK signaling pathway
cfr04012  ErbB signaling pathway
cfr04110  Cell cycle
cfr04115  p53 signaling pathway
cfr04370  VEGF signaling pathway
cfr04520  Adherens junction
KO pathway

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