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), https://www.phosphosite.org. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2828 CPTAC Assay Portal]
Authors
Oneshin , Kristina Hanspers , Zahra Roudbari , Anders Riutta , Egon Willighagen , Friederike Ehrhart , Eric Weitz , and Finterly HuActivity
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Cited In
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Organisms
Homo sapiensCommunities
CPTAC DiseasesAnnotations
Disease Ontology
bladder disease urinary bladder cancer cancer papillary renal cell carcinomaCell Type Ontology
bladder urothelial cellPathway Ontology
cancer pathway disease pathwayLabel | 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 | |
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 | |
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 | |
MMP2 | GeneProduct | ensembl:ENSG00000087245 | |
MMP9 | GeneProduct | ensembl:ENSG00000100985 | |
HBEGF | GeneProduct | ensembl:ENSG00000113070 | |
UPK3A | GeneProduct | ensembl:ENSG00000100373 | |
SRC | GeneProduct | ensembl:ENSG00000197122 | |
MAP2K1 | GeneProduct | ensembl:ENSG00000169032 | |
MAP2K2 | GeneProduct | ensembl:ENSG00000126934 | |
MAPK1 | GeneProduct | ensembl:ENSG00000100030 |
References
- KEGG Pathway: map05219
- 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
- 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
- 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
- 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
- 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
- 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