ArticleAging cell2014
Downregulation of the Werner syndrome protein induces a metabolic shift that compromises redox homeostasis and limits proliferation of cancer cells.
Article in Aging cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Extraordinary therapeutic effect of PSMA radioligand therapy in treatment-refractory progressive metastatic prostate cancer with the transketolase inhibitor benfo-oxythiamine as a radiosensitizer-A case report.Frontiers in medicine · 2024Article
- Peripheral neuropathies associated with DNA repair disorders.Muscle & nerve · 2023Review
- WRN promotes bone development and growth by unwinding SHOX-G-quadruplexes via its helicase activity in Werner Syndrome.Nature communications · 2022Article
- Genetic basis of cardiovascular aging is at the core of human longevity.The journal of cardiovascular aging · 2022Article
- Characterization of Stress Responses in aBiomolecules · 2021Article
- CDK2 phosphorylation of Werner protein (WRN) contributes to WRN's DNA double-strand break repair pathway choice.Aging cell · 2021Article
- Crosstalk among DNA Damage, Mitochondrial Dysfunction, Impaired Mitophagy, Stem Cell Attrition, and Senescence in the Accelerated Ageing Disorder Werner Syndrome.Cytogenetic and genome research · 2021Review
- WRN modulates translation by influencing nuclear mRNA export in HeLa cancer cells.BMC molecular and cell biology · 2020Article
- Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures.International journal of molecular sciences · 2020Review
- Incomplete Healing as a Cause of Aging: The Role of Mitochondria and the Cell Danger Response.Biology · 2019Review
- Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models.Molecules and cells · 2019Article
- Genetics and genomics in Peru: Clinical and research perspective.Molecular genetics & genomic medicine · 2018Review
- A systems genetics resource and analysis of sleep regulation in the mouse.PLoS biology · 2018Article
- EDIM-TKTL1/Apo10 Blood Test: An Innate Immune System Based Liquid Biopsy for the Early Detection, Characterization and Targeted Treatment of Cancer.International journal of molecular sciences · 2017Review
- Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress.Biochimica et biophysica acta · 2016Review
- TKTL1 expression in human malign and benign cell lines.BMC cancer · 2015Article
- Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells.BMC cancer · 2015Article
- Cellular deficiency of Werner syndrome protein or RECQ1 promotes genotoxic potential of hydroquinone and benzo[a]pyrene exposure.International journal of toxicologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The Werner syndrome protein (WRN) is a nuclear protein required for cell growth and proliferation. Loss-of-function mutations in the Werner syndrome gene are associated with the premature onset of age-related diseases. How loss of WRN limits cell proliferation and induces replicative senescence is poorly understood. Here, we show that WRN depletion leads to a striking metabolic shift that coordinately weakens the pathways that generate reducing equivalents for detoxification of reactive oxygen species and increases mitochondrial respiration. In cancer cells, this metabolic shift counteracts the Warburg effect, a defining characteristic of many malignant cells, resulting in altered redox balance and accumulation of oxidative DNA damage that inhibits cell proliferation and induces a senescence-like phenotype. Consistent with these findings, supplementation with antioxidant rescues at least in part cell proliferation and decreases senescence in WRN-knockdown cancer cells. These results demonstrate that WRN plays a critical role in cancer cell proliferation by contributing to the Warburg effect and preventing metabolic stress.
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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.