ArticleScientific reports2021
VHL suppresses RAPTOR and inhibits mTORC1 signaling in clear cell renal cell carcinoma.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Cabozantinib in combination with immune checkpoint inhibitors for renal cell carcinoma: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- From Genes to Proteins: The Indispensable Role of Proteogenomics in Advancing Clear Cell Renal Cell Carcinoma Research.International journal of molecular sciences · 2026Review
- Transient Overexpression of pVHL Mediated by Adenoviral Vector Injection in Pancreatic Tissue Decreases Blood Glucose Levels in a Hypercaloric Diet-Induced Mouse Model of Type 2 Diabetes Mellitus.International journal of molecular sciences · 2026Article
- Overview of clear cell renal cell carcinoma: from mechanisms to clinical.Frontiers in medicine · 2026Review
- T-CLASS: An Online Tool for the Identification and Classification of Aging and Senescence Using Transcriptome Data.Aging cell · 2025Article
- VHL ameliorates arecoline-induced oral submucosal fibrosis by promoting HDAC6 ubiquitination and blocking NF-κB pathway.Scientific reports · 2025Article
- Tumor-initiating and metastasis-initiating cells of clear-cell renal cell carcinoma.Journal of biomedical science · 2025Review
- Extensive genotype-phenotype heterogeneity in renal cell carcinoma - a proof-of-concept study.Frontiers in oncology · 2025Article
- Clinical features and mutational frequency of renal cell carcinoma from patients undergoing kidney transplant evaluation.Frontiers in oncology · 2025Article
- Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma.Nature reviews. Urology · 2024Review
- Genetics, Pathophysiology, and Current Challenges in Von Hippel-Lindau Disease Therapeutics.Diagnostics (Basel, Switzerland) · 2024Review
- Review
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Dysregulation of ubiquitination modification in renal cell carcinoma.Frontiers in genetics · 2024Review
- New Insights into the Link between SARS-CoV-2 Infection and Renal Cancer.Life (Basel, Switzerland) · 2023Review
- Article
- Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance.Cancers · 2023Review
- VHL tumor suppressor as a novel potential candidate biomarker in papillary thyroid carcinoma.Biomolecules & biomedicine · 2023Review
- Development and validation of a nomogram to evaluate the therapeutic effects of second-line axitinib in patients with metastatic renal cell carcinoma.Frontiers in oncology · 2023Article
- Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Inactivation of the tumor suppressor von Hippel-Lindau (VHL) gene is a key event in hereditary and sporadic clear cell renal cell carcinomas (ccRCC). The mechanistic target of rapamycin (mTOR) signaling pathway is a fundamental regulator of cell growth and proliferation, and hyperactivation of mTOR signaling is a common finding in VHL-dependent ccRCC. Deregulation of mTOR signaling correlates with tumor progression and poor outcome in patients with ccRCC. Here, we report that the regulatory-associated protein of mTOR (RAPTOR) is strikingly repressed by VHL. VHL interacts with RAPTOR and increases RAPTOR degradation by ubiquitination, thereby inhibiting mTORC1 signaling. Consistent with hyperactivation of mTORC1 signaling in VHL-deficient ccRCC, we observed that loss of vhl-1 function in C. elegans increased mTORC1 activity, supporting an evolutionary conserved mechanism. Our work reveals important new mechanistic insight into deregulation of mTORC1 signaling in ccRCC and links VHL directly to the control of RAPTOR/mTORC1. This may represent a novel mechanism whereby loss of VHL affects organ integrity and tumor behavior.
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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.