ArticleOncotarget2012
Targeting HIF2α translation with Tempol in VHL-deficient clear cell renal cell carcinoma.
Article in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- POLE2 of tumor cells promotes OPN secretion based on PCLAF to drive M2 macrophage polarization in clear cell renal cell carcinoma.Cancer gene therapy · 2026Article
- Rational Design of Non-Toxic Multidrug Combinations Demonstrates Durable and Hypoxia-Enhanced Efficacy Against Renal Cell Carcinoma.Pharmaceutics · 2025Article
- von-Hippel Lindau and Hypoxia-Inducible Factor at the Center of Renal Cell Carcinoma Biology.Hematology/oncology clinics of North America · 2023Review
- MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets.International journal of molecular sciences · 2022Article
- Looking for the Holy Grail-Drug Candidates for Glioblastoma Multiforme Chemotherapy.Biomedicines · 2022Review
- Activation and function of receptor tyrosine kinases in human clear cell renal cell carcinomas.BMC cancer · 2019Article
- Preclinical efficacy of dual mTORC1/2 inhibitor AZD8055 in renal cell carcinoma harboring a TFE3 gene fusion.BMC cancer · 2019Article
- TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease.Molecular cancer research : MCR · 2019Article
- Suppressive effects of iron chelation in clear cell renal cell carcinoma and their dependency on VHL inactivation.Free radical biology & medicine · 2019Article
- Translational repression of HIF2α expression in mice with Chuvash polycythemia reverses polycythemia.The Journal of clinical investigation · 2018Article
- Article
- Effect of Targeted Therapy With Pazopanib on Expression Levels of Transcription, Growth Factors and Components of AKT/m-TOR Signaling Pathway in Patients with Renal Cell CarcinomaAsian Pacific journal of cancer prevention : APJCP · 2017Article
- Role of Intestinal HIF-2α in Health and Disease.Annual review of physiology · 2016Review
- The Role of Hypoxia and Cancer Stem Cells in Renal Cell Carcinoma Pathogenesis.Stem cell reviews and reports · 2015Review
- Tonantzitlolone cytotoxicity toward renal cancer cells is PKCθ- and HSF1-dependent.Oncotarget · 2015Article
- New strategies in renal cell carcinoma: targeting the genetic and metabolic basis of disease.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Targeting ABL1-mediated oxidative stress adaptation in fumarate hydratase-deficient cancer.Cancer cell · 2014Article
- KRAS and DAXX/ATRX gene mutations are correlated with the clinicopathological features, advanced diseases, and poor prognosis in Chinese patients with pancreatic neuroendocrine tumors.International journal of biological sciences · 2014Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The tumor suppressor gene, Von Hippel-Lindau (VHL), is frequently mutated in the most common form of kidney cancer, clear cell renal cell carcinoma (CCRCC). In hypoxic conditions, or when there is a VHL mutation, the hypoxia inducible factors, HIF1α and HIF2α, are stabilized and transcribe a panel of genes associated with cancer such as vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor (PDGF), and glucose transporter 1 (GLUT1). Recent studies in clear cell kidney cancer have suggested that HIF2α, but not HIF1α, is the critical oncoprotein in the VHL pathway. Therefore, targeting HIF2α could provide a potential therapeutic approach for patients with advanced CCRCC. Since iron regulatory protein 1 (IRP1) is known to inhibit the translation of HIF2α, we investigated whether Tempol, a stable nitroxide that activates IRP1 towards IRE-binding, might have a therapeutic effect on a panel of human CCRCC cells expressing both HIF1α and HIF2α. We first evaluated the protein expression of HIF1α and HIF2α in 15 different clear cell renal carcinoma cell lines established from patient tumors in our laboratory. Tempol decreased the expression of HIF2α, and its downstream targets in all the cell lines of the panel. This effect was attributed to a dramatic increase of IRE-binding activity of IRP1. Several cell lines were found to have an increased IRP1 basal activity at 20% O2 compared to 5% O2, which may lower HIF2α expression in some of the cell lines in a VHL-independent manner. Taken together our data identify Tempol as an agent with potential therapeutic activity targeting expression of HIF2α in VHL-deficient clear cell kidney cancer and illustrate the importance of studying biochemical processes at relevant physiological O2 levels.
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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.