ArticlePloS one2013
Fibroblast growth factor receptors-1 and -3 play distinct roles in the regulation of bladder cancer growth and metastasis: implications for therapeutic targeting.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Meta-Analysis of the Luminal and Basal Subtypes of Bladder Cancer and the Identification of Signature Immunohistochemical Markers for Clinical Use.EBioMedicine · 2016Pooled it
- The Role of FGFR3 in the Progression of Bladder Cancer.Cancers · 2025Article
- Characterization of cancer-related fibroblasts in bladder cancer and construction of CAFs-based bladder cancer classification: insights from single-cell and multi-omics analysis.Frontiers in immunology · 2025Article
- The roles of FGFR3 and c-MYC in urothelial bladder cancer.Discover oncology · 2024Review
- New Perspectives on the Role of Liquid Biopsy in Bladder Cancer: Applicability to Precision Medicine.Cancers · 2024Review
- Sialidase NEU3 Contributes to the Invasiveness of Bladder Cancer.Biomedicines · 2024Article
- Homeobox Gene Expression Dysregulation as Potential Diagnostic and Prognostic Biomarkers in Bladder Cancer.Diagnostics (Basel, Switzerland) · 2023Review
- Development of resistance to FGFR inhibition in urothelial carcinoma via multiple pathways in vitro.The Journal of pathology · 2023Article
- Article
- TNM staging towards a personalized approach in metastatic urothelial carcinoma: what will the future be like?-a narrative review.Translational andrology and urology · 2021Review
- Management of Clinically Regional Node-Positive Urothelial Carcinoma of the Bladder.Current oncology reports · 2021Review
- Tumor heterogeneity and the potential role of liquid biopsy in bladder cancer.Cancer communications (London, England) · 2021Review
- Classification of bladder cancer cell lines according to regulon activity.Turkish journal of biology = Turk biyoloji dergisi · 2021Article
- 2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology.Journal of oncology · 2021Review
- Tumor heterogeneity in muscle-invasive bladder cancer.Translational andrology and urology · 2020Review
- Assessment of Luminal and Basal Phenotypes in Bladder Cancer.Scientific reports · 2020Article
- Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma.Cancers · 2020Review
- Updates on mechanistic insights and targeting of tumour metastasis.Journal of cellular and molecular medicine · 2020Review
- Targeting FGFR overcomes EMT-mediated resistance in EGFR mutant non-small cell lung cancer.Oncogene · 2019Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Fibroblast growth factor receptors (FGFRs) are activated by mutation and overexpressed in bladder cancers (BCs), and FGFR inhibitors are currently being evaluated in clinical trials in BC patients. However, BC cells display marked heterogeneity in their responses to FGFR inhibitors, and the biological mechanisms underlying this heterogeneity are not well defined. Here we used a novel inhibitor of FGFRs 1-3 and RNAi to determine the effects of inhibiting FGFR1 or FGFR3 in a panel of human BC cell lines. We observed that FGFR1 was expressed in BC cells that also expressed the "mesenchymal" markers ZEB1 and vimentin, whereas FGFR3 expression was restricted to the E-cadherin- and p63-positive "epithelial" subset. Sensitivity to the growth-inhibitory effects of BGJ-398 was also restricted to the "epithelial" BC cells and it correlated directly with FGFR3 mRNA levels but not with the presence of activating FGFR3 mutations. In contrast, BGJ-398 did not strongly inhibit proliferation but did block invasion in the "mesenchymal" BC cells in vitro. Similarly, BGJ-398 did not inhibit primary tumor growth but blocked the production of circulating tumor cells (CTCs) and the formation of lymph node and distant metastases in mice bearing orthotopically implanted "mesenchymal" UM-UC3 cells. Together, our data demonstrate that FGFR1 and FGFR3 have largely non-overlapping roles in regulating invasion/metastasis and proliferation in distinct "mesenchymal" and "epithelial" subsets of human BC cells. The results suggest that the tumor EMT phenotype will be an important determinant of the biological effects of FGFR inhibitors in patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.