Bladder cancer (WP2828)

Homo sapiens

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 carcinomas are bladder carcinomas, and urothelial carcinomas of the renal pelvis and ureter account for only approximately 7% of the total. Urothelial tumors arise and evolve through divergent phenotypic pathways. Some tumors progress from urothelial hyperplasia to low-grade non-invasive superficial papillary tumors. More aggressive variants arise either from flat, high-grade carcinoma in situ (CIS) and progress to invasive tumors, or they arise de novo as invasive tumors. 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 tumor microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF). Phosphorylation sites were added based on information from PhosphoSitePlus (R), Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


Oneshin , Kristina Hanspers , Zahra Roudbari , Anders Riutta , Egon Willighagen , Friederike Ehrhart , Eric Weitz , and Finterly Hu


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Homo sapiens


CPTAC Diseases


Disease Ontology

bladder disease urinary bladder cancer cancer papillary renal cell carcinoma

Cell Type Ontology

bladder urothelial cell

Pathway Ontology

cancer pathway disease pathway


Label Type Compact URI Comment
DAPK1 GeneProduct ncbigene:1612
CCND1 GeneProduct ncbigene:595
E2F1 GeneProduct ncbigene:1869
VEGFA GeneProduct ncbigene:7422
FGFR3 GeneProduct ensembl:ENSG00000068078
EGF GeneProduct ensembl:ENSG00000138798
C-MYC GeneProduct ncbigene:4609
CDH1 GeneProduct ncbigene:999
DAPK2 GeneProduct ncbigene:23604
THBS1 GeneProduct ncbigene:7057
EGFR GeneProduct ncbigene:1956
CDKN1A GeneProduct ncbigene:1026
MSK1 GeneProduct ncbigene:9252
CDKN2A GeneProduct ncbigene:1029
CDKN2A GeneProduct ncbigene:1029
IL8 GeneProduct ncbigene:3576
ERBB2 GeneProduct ncbigene:2064
p85-Beta GeneProduct ncbigene:5296
MMP1 GeneProduct ncbigene:4312
BRAF GeneProduct ncbigene:673
MDM2 GeneProduct ncbigene:4193
DAPK3 GeneProduct ncbigene:1613
HRAS GeneProduct ncbigene:3265
TP53 GeneProduct ncbigene:7157
TYMP GeneProduct ncbigene:1890
RB1 GeneProduct ncbigene:5925
HRAS GeneProduct ncbigene:3265
p85-ALPHA GeneProduct ncbigene:5295
RASSF1 GeneProduct ncbigene:11186
CDK4 GeneProduct ncbigene:1019
NRAS GeneProduct ensembl:ENSG00000213281
KRAS GeneProduct ensembl:ENSG00000133703
RAF1 GeneProduct ensembl:ENSG00000132155
ARAF GeneProduct ensembl:ENSG00000078061
DAPK1 GeneProduct ncbigene:1612
DAPK2 GeneProduct ncbigene:23604
DAPK3 GeneProduct ncbigene:1613
RASSF1 GeneProduct ncbigene:11186
MMP2 GeneProduct ensembl:ENSG00000087245
MMP9 GeneProduct ensembl:ENSG00000100985
HBEGF GeneProduct ensembl:ENSG00000113070
UPK3A GeneProduct ensembl:ENSG00000100373
SRC GeneProduct ensembl:ENSG00000197122
MMP2 GeneProduct ensembl:ENSG00000087245
MMP9 GeneProduct ensembl:ENSG00000100985
MAP2K1 GeneProduct ensembl:ENSG00000169032
MAP2K2 GeneProduct ensembl:ENSG00000126934
MAPK1 GeneProduct ensembl:ENSG00000100030


  1. KEGG Pathway: map05219
  2. Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer. Wolff EM, Liang G, Jones PA. Nat Clin Pract Urol. 2005 Oct;2(10):502–10. PubMed Europe PMC Scholia
  3. Mutations in FGFR3 and PIK3CA, singly or combined with RAS and AKT1, are associated with AKT but not with MAPK pathway activation in urothelial bladder cancer. Juanpere N, Agell L, Lorenzo M, de Muga S, López-Vilaró L, Murillo R, et al. Hum Pathol. 2012 Oct;43(10):1573–82. PubMed Europe PMC Scholia
  4. A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges. di Martino E, Tomlinson DC, Knowles MA. Adv Urol. 2012;2012:429213. PubMed Europe PMC Scholia
  5. Oncogenic FGFR3 gene fusions in bladder cancer. Williams SV, Hurst CD, Knowles MA. Hum Mol Genet. 2013 Feb 15;22(4):795–803. PubMed Europe PMC Scholia
  6. PI3K/AKT pathway activation in bladder carcinogenesis. Calderaro J, Rebouissou S, de Koning L, Masmoudi A, Hérault A, Dubois T, et al. Int J Cancer. 2014 Apr 15;134(8):1776–84. PubMed Europe PMC Scholia
  7. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia