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
fibroblast growth factor receptor 3 [EC:
A-Raf proto-oncogene serine/threonine-protein kinase [EC:
B-Raf proto-oncogene serine/threonine-protein kinase [EC:
RAF proto-oncogene serine/threonine-protein kinase [EC:
mitogen-activated protein kinase kinase 1 [EC:
mitogen-activated protein kinase kinase 2 [EC:
mitogen-activated protein kinase 1/3 [EC:
ribosomal protein S6 kinase alpha-5 [EC:
Myc proto-oncogene protein
Ras association domain-containing protein 1
death-associated protein kinase [EC:
cyclin-dependent kinase inhibitor 2A
E3 ubiquitin-protein ligase Mdm2 [EC:
tumor protein p53
cyclin-dependent kinase inhibitor 1A
cyclin-dependent kinase 4 [EC:
transcription factor E2F1
transcription factor E2F2
transcription factor E2F3
heparin-binding EGF-like growth factor
matrix metalloproteinase-2 (gelatinase A) [EC:
matrix metalloproteinase-9 (gelatinase B) [EC:
tyrosine-protein kinase Src [EC:
epidermal growth factor
receptor tyrosine-protein kinase erbB-2 [EC:
epidermal growth factor receptor [EC:
thymidine phosphorylase [EC:
vascular endothelial growth factor A
matrix metalloproteinase-1 (interstitial collagenase) [EC:
cadherin 1, type 1, E-cadherin
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MAPK signaling pathway
ErbB signaling pathway
p53 signaling pathway
VEGF signaling pathway
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