ArticleProceedings of the National Academy of Sciences of the United States of America2006
The von Hippel-Lindau tumor suppressor gene product represses oncogenic beta-catenin signaling in renal carcinoma cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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
40 citing papers in PubMed, 95 citations in OpenAlex.
- Molecular landscape of clear cell renal cell carcinoma: targeting the Wnt/β-catenin signaling pathway.Discover oncology · 2025Review
- Review
- Mutation of the proline P81 into a serine modifies the tumour suppressor function of the von Hippel-Lindau gene in the ccRCC.British journal of cancer · 2022Article
- Immunohistochemical analysis of beta-catenin expression: a probable prognostic marker and potential therapeutic target in renal cell carcinoma.Medicine and pharmacy reports · 2021Article
- Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients.Nature communications · 2020Article
- Adenoviral delivery of VHL suppresses bone sarcoma cell growth through inhibition of Wnt/β-catenin signaling.Cancer gene therapy · 2019Article
- Article
- Inhibition of canonical WNT/β-catenin signaling is involved in leflunomide (LEF)-mediated cytotoxic effects on renal carcinoma cells.Oncotarget · 2016Article
- Wnt Signaling in Renal Cell Carcinoma.Cancers · 2016Review
- The expression and function of Frizzled-7 in human renal cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Article
- MET Inhibition in Clear Cell Renal Cell Carcinoma.Journal of Cancer · 2016Article
- MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors.BioMed research international · 2015Article
- Binning somatic mutations based on biological knowledge for predicting survival: an application in renal cell carcinoma.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2015Article
- Met in urological cancers.Cancers · 2014Review
- Synergistic signaling of tumor cell invasiveness by hepatocyte growth factor and hypoxia.The Journal of biological chemistry · 2014Article
- Proliferation inhibition and the underlying molecular mechanisms of microRNA-30d in renal carcinoma cells.Oncology letters · 2014Article
- Molecular signatures in urologic tumors.International journal of molecular sciences · 2013Review
- Receptor tyrosine kinase-like orphan receptor 2 (Ror2) expression creates a poised state of Wnt signaling in renal cancer.The Journal of biological chemistry · 2013Article
- Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.PloS one · 2013Article
- Renal cancer: oxygen meets metabolism.Experimental cell research · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic clear cell renal cell carcinoma (RCC), resulting in the aberrant expression of genes that control cell proliferation, invasion, and angiogenesis. The molecular mechanisms by which VHL loss leads to tumorigenesis are not yet fully defined. VHL loss has been shown to allow robust RCC cell motility, invasiveness, and morphogenesis in response to hepatocyte growth factor (HGF) stimulation, processes that are known to contribute to tumor invasiveness and metastatic potential. Among the most likely intracellular mediators of these HGF-driven activities is beta-catenin, a structural link between cadherens and the actin cytoskeleton, as well as a gene transactivator. We show that reconstitution of VHL expression in RCC cells repressed HGF-stimulated beta-catenin tyrosyl phosphorylation, adherens junction disruption, cytoplasmic beta-catenin accumulation, and reporter gene transactivation in RCC cells. Ectopic expression of a ubiquitination-resistant beta-catenin mutant specifically restored HGF-stimulated invasion and morphogenesis in VHL-transfected RCC cells. VHL gene silencing in non-RCC renal epithelial cells phenotypically mimicked VHL loss in RCC, and HGF-driven invasiveness was blocked by the expression of a dominant-negative mutant of Tcf. We conclude that, unlike many other cancers, where HGF pathway activation contributes to malignancy through the acquisition of autocrine signaling, receptor overexpression, or mutation, in RCC cells VHL loss enables HGF-driven oncogenic beta-catenin signaling. These findings identify beta-catenin as a potential target in biomarker and drug development for RCC.
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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.