ArticleCell death & disease2019
von Hippel-Lindau mutants in renal cell carcinoma are regulated by increased expression of RSUME.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Association of hypoxia-inducible factor-1α (HIF1α) 1790G/A gene polymorphism with renal cell carcinoma and prostate cancer susceptibility: a meta-analysis.BMC medical genetics · 2019Pooled it
- Impact of Hypoxia-Inducible Factor-1α Gene Polymorphisms on Renal Cell Carcinoma Susceptibility in a Chinese Han Population.Lifestyle genomics · 2026Article
- TCEB2/HIF1A signaling axis promotes chemoresistance in ovarian cancer cells by enhancing glycolysis and angiogenesis.European journal of medical research · 2024Article
- Genetics, Pathophysiology, and Current Challenges in Von Hippel-Lindau Disease Therapeutics.Diagnostics (Basel, Switzerland) · 2024Review
- The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications.Experimental hematology & oncology · 2023Review
- An In Vitro Analysis of TKI-Based Sequence Therapy in Renal Cell Carcinoma Cell Lines.International journal of molecular sciences · 2023Article
- EHD2, a novel HIF target gene, is a promising biomarker in clear cell renal cell carcinoma.International journal of clinical and experimental pathology · 2023Article
- VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells.Cell & bioscience · 2022Article
- Review
- Impact of RSUME Actions on Biomolecular Modifications in Physio-Pathological Processes.Frontiers in endocrinology · 2022Review
- Review
- Clinical and Laboratory Characteristics of a Large Iranian Kindred Afflicted with Von Hippel Lindau Disease.International journal of endocrinology and metabolism · 2021Article
- A Precision Strategy to Cure Renal Cell Carcinoma by Targeting Transglutaminase 2.International journal of molecular sciences · 2020Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
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Abstract
Renal cell carcinoma (RCC) is the major cause of death among patients with von Hippel-Lindau (VHL) disease. Resistance to therapies targeting tumor angiogenesis opens the question about the underlying mechanisms. Previously we have described that RWDD3 or RSUME (RWD domain-containing protein SUMO Enhancer) sumoylates and binds VHL protein and negatively regulates HIF degradation, leading to xenograft RCC tumor growth in mice. In this study, we performed a bioinformatics analysis in a ccRCC dataset showing an association of RSUME levels with VHL mutations and tumor progression, and we demonstrate the molecular mechanism by which RSUME regulates the pathologic angiogenic phenotype of VHL missense mutations. We report that VHL mutants fail to downregulate RSUME protein levels accounting for the increased RSUME expression found in RCC tumors. Furthermore, we prove that targeting RSUME in RCC cell line clones carrying missense VHL mutants results in decreased early tumor angiogenesis. The mechanism we describe is that RSUME sumoylates VHL mutants and beyond its sumoylation capacity, interacts with Type 2 VHL mutants, reduces HIF-2α-VHL mutants binding, and negatively regulates the assembly of the Type 2 VHL, Elongins and Cullins (ECV) complex. Altogether these results show RSUME involvement in VHL mutants deregulation that leads to the angiogenic phenotype of RCC tumors.
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