ArticleScientific reports2016
CRISPR-Mediated VHL Knockout Generates an Improved Model for Metastatic Renal Cell Carcinoma.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 76 citations in OpenAlex.
- Epithelial-Mesenchymal Transition Markers in Clear Cell Renal Cell Carcinoma: Expression Patterns and Prognostic Significance.Journal of personalized medicine · 2026Article
- Epithelial-mesenchymal transition and sunitinib resistance in renal cell carcinoma: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2026Review
- Strategic trimodal therapy enhances radiation-induced abscopal response in renal cancer.Journal of translational medicine · 2025Article
- Multimodal targeting of metastatic renal cell carcinoma via CD70-directed allogeneic CAR-NKT cells.Cell reports. Medicine · 2025Article
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- An Exogenous Ketone Ester Slows Tumor Progression in Murine Breast and Renal Cancer Models.Cancers · 2024Article
- Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone.Cancer research communications · 2024Article
- VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis.The Journal of clinical investigation · 2024Article
- The 5th Kidney Cancer Research Summit: Research Accelerating Cures for Renal Cell Carcinoma in 2023.The oncologist · 2024Article
- Article
- Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma.International journal of molecular sciences · 2023Article
- Synthesis of the Hypoxia-Inducible Factor-2Tetrahedron letters · 2023Article
- VHL L169P Variant Does Not Alter Cellular Hypoxia Tension in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2023Article
- Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma.Signal transduction and targeted therapy · 2023Article
- A Mesenchymal Tumor Cell State Confers Increased Dependency on the BCL-XL Antiapoptotic Protein in Kidney Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy.International journal of molecular sciences · 2022Article
- VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells.Cell & bioscience · 2022Article
- Article
- Listeria-based immunotherapy directed against CD105 exerts anti-angiogenic and anti-tumor efficacy in renal cell carcinoma.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Metastatic renal cell carcinoma (mRCC) is nearly incurable and accounts for most of the mortality associated with RCC. Von Hippel Lindau (VHL) is a tumour suppressor that is lost in the majority of clear cell RCC (ccRCC) cases. Its role in regulating hypoxia-inducible factors-1α (HIF-1α) and -2α (HIF-2α) is well-studied. Recent work has demonstrated that VHL knock down induces an epithelial-mesenchymal transition (EMT) phenotype. In this study we showed that a CRISPR/Cas9-mediated knock out of VHL in the RENCA model leads to morphologic and molecular changes indicative of EMT, which in turn drives increased metastasis to the lungs. RENCA cells deficient in HIF-1α failed to undergo EMT changes upon VHL knockout. RNA-seq revealed several HIF-1α-regulated genes that are upregulated in our VHL knockout cells and whose overexpression signifies an aggressive form of ccRCC in the cancer genome atlas (TCGA) database. Independent validation in a new clinical dataset confirms the upregulation of these genes in ccRCC samples compared to adjacent normal tissue. Our findings indicate that loss of VHL could be driving tumour cell dissemination through stabilization of HIF-1α in RCC. A better understanding of the mechanisms involved in this phenomenon can guide the search for more effective treatments to combat mRCC.
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Registered trials
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