ArticleBMC cancer2014
Canonical Notch signalling is inactive in urothelial carcinoma.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Bladder Cancer: Uncovering the Predictive Role of NOTCH as an Emerging Candidate Biomarker for Therapeutic Strategies.Cancers · 2025Review
- The urothelial gene regulatory network: understanding biology to improve bladder cancer management.Oncogene · 2024Review
- Article
- Systems Drug Design for Muscle Invasive Bladder Cancer and Advanced Bladder Cancer by Genome-Wide Microarray Data and Deep Learning Method with Drug Design Specifications.International journal of molecular sciences · 2022Article
- RITA1 drives the growth of bladder cancer cells by recruiting TRIM25 to facilitate the proteasomal degradation of RBPJ.Cancer science · 2022Article
- Development, regeneration and tumorigenesis of the urothelium.Development (Cambridge, England) · 2022Review
- Article
- Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Therapeutic and prognostic implications of NOTCH and MAPK signaling in bladder cancer.Cancer science · 2021Article
- Article
- Urothelial organoids originating from Cd49fNature communications · 2019Article
- Unravelling disparate roles of NOTCH in bladder cancer.Nature reviews. Urology · 2018Review
- Loss of nuclear NOTCH1, but not its negative regulator NUMB, is an independent predictor of cervical malignancy.Oncotarget · 2018Article
- Decitabine, a DNA-demethylating agent, promotes differentiation via NOTCH1 signaling and alters immune-related pathways in muscle-invasive bladder cancer.Cell death & disease · 2017Article
- Notch3 overexpression enhances progression and chemoresistance of urothelial carcinoma.Oncotarget · 2017Article
- Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes.Nature genetics · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNotch signalling regulates cell fate in most tissues, promoting precursor cell proliferation in some, but differentiation in others. Accordingly, downregulation or overactivity variously contributes to cancer development. So far, little is known about Notch pathway activity and function in the normal urothelium and in urothelial carcinoma (UC). We have therefore investigated expression of Notch pathway components in UC tissues and cell lines and studied the function of one receptor, NOTCH1, in detail.
methodsExpression of canonical Notch pathway components were studied in UC and normal bladder tissues by immunohistochemistry and quantitative RT-PCR and in UC cell lines and normal cultured urothelial cells by qRT-PCR, immunocytochemistry and Western blotting. Pathway activity was measured by reporter gene assays. Its influence on cell proliferation was investigated by γ-secretase inhibition. Effects of NOTCH1 restoration were followed by measuring cell cycle distribution, proliferation, clonogenicity and nuclear morphology.
resultsNOTCH1 and its ligand, DLL1, were expressed at plasma membranes and in the cytoplasm of cells in the upper normal urothelium layer, but became downregulated in UC tissues, especially in high-stage tumours. In addition, the proteins were often delocalized intracellularly. According differences were observed in UC cell lines compared to normal urothelial cells. Canonical Notch pathway activity in reporter assays was repressed in UC cell lines compared to normal cells and a mammary carcinoma cell line, but was induced by transfected NOTCH1. Inhibitors of Notch signalling acting at the γ-secretase step did not affect UC cell proliferation at concentrations efficacious against a cell line with known Notch activity. Surprisingly, overexpression of NOTCH1 into UC cell lines did not significantly affect short-term cell proliferation, but induced nuclear abnormalities and diminished clonogenicity.
conclusionOur data indicate that canonical Notch signalling is suppressed in urothelial carcinoma mainly through downregulation of NOTCH1. These findings can be explained by proposing that canonical Notch signalling may promote differentiation in the urothelium, like in many squamous epithelia, and its suppression may therefore be advantageous for tumour progression. As an important corollary, inhibition of canonical Notch signalling is unlikely to be efficacious and might be counter-productive in the treatment of urothelial carcinoma.
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