ArticleMolecular and cellular biology2010
Renal oxygenation suppresses VHL loss-induced senescence that is caused by increased sensitivity to oxidative stress.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Mechanisms of resistance to VHL loss-induced genetic and pharmacological vulnerabilities.EMBO molecular medicine · 2026Article
- Oncogenic Cell Tagging and Single-Cell Transcriptomics Reveal Cell Type-Specific and Time-Resolved Responses to Vhl Inactivation in the Kidney.Cancer research · 2024Article
- Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins.Cell reports · 2021Article
- HIF-1α and HIF-2α differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice.Nature communications · 2020Article
- Lamin-B1 is a senescence-associated biomarker in clear-cell renal cell carcinoma.Oncology letters · 2019Article
- A prospect of cell immortalization combined with matrix microenvironmental optimization strategy for tissue engineering and regeneration.Cell & bioscience · 2019Review
- MicroRNA-21-5p induces the metastatic phenotype of human cervical carcinoma cellsOncology letters · 2018Article
- Loss of PBRM1 rescues VHL dependent replication stress to promote renal carcinogenesis.Nature communications · 2017Article
- Vhl deletion in renal epithelia causes HIF-1α-dependent, HIF-2α-independent angiogenesis and constitutive diuresis.Oncotarget · 2016Article
- Gadd45b deficiency promotes premature senescence and skin aging.Oncotarget · 2016Article
- Clinical strategies and animal models for developing senolytic agents.Experimental gerontology · 2015Article
- Hypoxia-induced SUMOylation of E3 ligase HAF determines specific activation of HIF2 in clear-cell renal cell carcinoma.Cancer research · 2015Article
- VHL, the story of a tumour suppressor gene.Nature reviews. Cancer · 2015Review
- Expression of glutamine transporter Slc38a3 (SNAT3) during acidosis is mediated by a different mechanism than tissue-specific expression.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2014Article
- SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer.Cancer cell · 2013Article
- Cross-talk between HIF and p53 as mediators of molecular responses to physiological and genotoxic stresses.Molecular cancer · 2013Review
- Combined mutation of Vhl and Trp53 causes renal cysts and tumours in mice.EMBO molecular medicine · 2013Article
- The VHL/HIF axis in clear cell renal carcinoma.Seminars in cancer biology · 2013Review
- Renal cancer: oxygen meets metabolism.Experimental cell research · 2012Review
- Prospective experimental studies on the renal protective effect of ulinastatin after paraquat poisoning.World journal of emergency medicine · 2012Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Loss of the VHL tumor suppressor is regarded as an initiating event in the development of clear-cell renal carcinoma. Surprisingly, loss of VHL induces senescence in mouse fibroblasts in vitro, a response that would restrict development of renal carcinoma in vivo. Typical in vitro cell culture levels of oxygen, however, are significantly higher than physiological levels of oxygen, which have been shown to abrogate senescence induced by many stimuli. Therefore, we investigated the oxygen dependence of VHL loss-induced senescence. Using mouse fibroblasts and primary renal epithelial cells in vitro, we found that VHL loss leads to senescence under atmospheric conditions (21% O(2)), partly through increasing p27 levels, but not under physiological oxygenation (2% to 5% O(2)), despite maintaining increased p27 expression. This suggests that VHL inactivation sensitizes cells to oxidative stress. In support of this concept, senescence following VHL loss depends on p53 activity, which decreases under the less stressful conditions of mild hypoxia. We confirmed these observations in vivo by treating kidney-specific VHL knockout animals with the potent oxidizer paraquat and observed a robust induction of cellular senescence. Together, these data demonstrate that in vivo oxygenation promotes tolerance of VHL loss in renal epithelia, which may promote the development of renal carcinoma.
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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.