Bladder Cancer (Homo sapiens)

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33333533333333Urothelial cellNucleusEndothelial cell migrationOxidative stressG1/S ProgressionNormal urotheliumPromoter methylationEndothelial Cell proliferationDegradation of extracellular matrixReduced expressionChemoattraction of endothelial cellsDefect in cell-cell adhesionCDKN2AAdherens junctionMAPK Signaling PathwayHRASE2F1VEGFARASSF1MDM2PI3KCCND1VEGF Signaling PathwayCDH1CDKN2AEGFDAPK2DAPK3p53 signaling pathwayTYMPCDKN1ACell CycleDAPK1HRASErbB Signaling PathwayTP53FGFR3MSK1THBS1ERBB2p85-BetaEGFRBRAFMMP1C-MYCRB1IL8p85-ALPHAAngiogenesisP21, 4, 6PCDK4HyperplasiaLow-gradenon-invasivepapillary tumourRecurrenceInvasive tumour(High-grade)MetastasisCIS / DysplasiaNormalurotheliumNRASKRASRAF1ARAFDAPK1DAPK2DAPK3RASSF1MMP2MMP9333HBEGFUPK3ASRCMMP2MMP9LegendActivating mutationInactivating mutationMAP2K1PMAP2K2PPPMAPK1PP


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). Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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  1. di Martino E, Tomlinson DC, Knowles MA; ''A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges.''; Adv Urol, 2012 PubMed Europe PMC Scholia
  2. Juanpere N, Agell L, Lorenzo M, de Muga S, Lأ³pez-Vilarأ³ L, Murillo R, Mojal S, Serrano S, Lorente JA, Lloreta J, Hernأ،ndez S; ''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.''; Hum Pathol, 2012 PubMed Europe PMC Scholia
  3. ''Bladder Cancer Pathway'';,
  4. Wolf EM, Liang G, Jones PA; ''Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer.'';, 2005 PubMed Europe PMC Scholia
  5. Calderaro J, Rebouissou S, de Koning L, Masmoudi A, Hأ©rault A, Dubois T, Maille P, Soyeux P, Sibony M, de la Taille A, Vordos D, Lebret T, Radvanyi F, Allory Y; ''PI3K/AKT pathway activation in bladder carcinogenesis.''; Int J Cancer, 2014 PubMed Europe PMC Scholia
  6. Williams SV, Hurst CD, Knowles MA; ''Oncogenic FGFR3 gene fusions in bladder cancer.''; Hum Mol Genet, 2013 PubMed Europe PMC Scholia


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108113view10:20, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
106313view17:48, 20 August 2019KhanspersModified description
105669view18:13, 12 August 2019EgonwFixed a WikiPathways identifier.
105442view04:54, 8 August 2019KhanspersModified description
105002view04:53, 28 June 2019KhanspersModified description
104855view14:56, 20 June 2019FehrhartRB1 binds E2F1
104854view14:54, 20 June 2019Fehrhart
103783view20:30, 5 April 2019Khanspersmoved lit refs from state to parent node
103770view00:54, 5 April 2019Khanspersaded literature references
98708view10:46, 30 September 2018EgonwRegular arrow type.
98683view00:31, 28 September 2018KhanspersOntology Term : 'bladder urothelial cell' added !
98682view00:30, 28 September 2018KhanspersOntology Term : 'urinary bladder cancer' added !
98681view00:29, 28 September 2018Khanspersadded phosphosite info
98680view00:13, 28 September 2018Khanspersupdates
97129view18:34, 30 April 2018KhanspersOntology Term : 'papillary renal cell carcinoma' added !
89143view21:56, 22 August 2016AriuttaOntology Term : 'disease pathway' added !
87377view11:05, 22 July 2016MaintBotadded missing graphids
79529view11:42, 24 March 2015Zariadd ID for p85 gene
78868view23:01, 9 February 2015MaintBotadded xrefs
78553view10:31, 7 January 2015MaintBotadded missing graphIds
78174view18:46, 8 December 2014Khanspersupdate
78133view20:18, 4 December 2014KhanspersAdded content
78132view20:02, 4 December 2014KhanspersOntology Term : 'bladder disease' added !
78131view20:02, 4 December 2014KhanspersOntology Term : 'cancer' added !
78130view20:00, 4 December 2014KhanspersModified description
78129view19:59, 4 December 2014KhanspersAdded xrefs, changed layout
76266view13:48, 25 June 2014OneshinPeriodical save, work in progress
76265view13:27, 25 June 2014OneshinPeriodical save, work in progress
76260view16:29, 24 June 2014OneshinWork in Progress
76259view16:28, 24 June 2014OneshinNew pathway

External references


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NameTypeDatabase referenceComment
ARAFGeneProductENSG00000078061 (Ensembl)
Adherens junction Pathway
AngiogenesisPathwayWP1539 (WikiPathways)
BRAFGeneProduct673 (Entrez Gene)
C-MYCGeneProduct4609 (Entrez Gene)
CCND1GeneProduct595 (Entrez Gene)
CDH1GeneProduct999 (Entrez Gene)
CDK4GeneProduct1019 (Entrez Gene)
CDKN1AGeneProduct1026 (Entrez Gene)
CDKN2AGeneProduct1029 (Entrez Gene)
Cell Cycle PathwayWP179 (WikiPathways)
DAPK1GeneProduct1612 (Entrez Gene)
DAPK2GeneProduct23604 (Entrez Gene)
DAPK3GeneProduct1613 (Entrez Gene)
E2F1GeneProduct1869 (Entrez Gene)
EGFGeneProductENSG00000138798 (Ensembl)
EGFRGeneProduct1956 (Entrez Gene)
ERBB2GeneProduct2064 (Entrez Gene)
ErbB Signaling PathwayPathwayWP673 (WikiPathways)
FGFR3GeneProductENSG00000068078 (Ensembl)
HBEGFGeneProductENSG00000113070 (Ensembl)
HRASGeneProduct3265 (Entrez Gene)
IL8GeneProduct3576 (Entrez Gene)
KRASGeneProductENSG00000133703 (Ensembl)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAPK Signaling PathwayPathwayWP382 (WikiPathways)
MAPK1GeneProductENSG00000100030 (Ensembl)
MDM2GeneProduct4193 (Entrez Gene)
MMP1GeneProduct4312 (Entrez Gene)
MMP2GeneProductENSG00000087245 (Ensembl)
MMP9GeneProductENSG00000100985 (Ensembl)
MSK1GeneProduct9252 (Entrez Gene)
NRASGeneProductENSG00000213281 (Ensembl)
RAF1GeneProductENSG00000132155 (Ensembl)
RASSF1GeneProduct11186 (Entrez Gene)
RB1GeneProduct5925 (Entrez Gene)
SRCGeneProductENSG00000197122 (Ensembl)
THBS1GeneProduct7057 (Entrez Gene)
TP53GeneProduct7157 (Entrez Gene)
TYMPGeneProduct1890 (Entrez Gene)
UPK3AGeneProductENSG00000100373 (Ensembl)
VEGF Signaling PathwayPathwayWP1919 (WikiPathways)
VEGFAGeneProduct7422 (Entrez Gene)
p53 signaling pathwayPathwayWP1742 (WikiPathways)
p85-ALPHAGeneProduct5295 (Entrez Gene)
p85-BetaGeneProduct5296 (Entrez Gene)

Annotated Interactions

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