ArticleCell death and differentiation2012
PON3 is upregulated in cancer tissues and protects against mitochondrial superoxide-mediated cell death.
Article in Cell death and differentiation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
54 citing papers in PubMed, 89 citations in OpenAlex.
- Downregulation of paraoxonase 3 contributes to aggressive human hepatocellular carcinoma progression and associates with poor prognosis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Trial
- Epigenomic characterization of locally advanced anal cancer: a radiation therapy oncology group 98-11 specimen study.Diseases of the colon and rectum · 2014Trial
- Paraoxonases as metabolic and signaling modulators: prospects for therapeutic and preventive implications.npj metabolic health and disease · 2026Review
- Targeted proteomics of extreme vascular phenotypes in type 1 diabetes: the ESCAPER study.Cardiovascular diabetology · 2026Article
- Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk.bioRxiv : the preprint server for biology · 2026Article
- The Paraoxonase (International journal of molecular sciences · 2025Review
- Dnmt1 Alleviates S1PR1-Mediated Pyroptosis after Spinal Cord Injury through Regulating Pon3 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Analysis of Plasma Proteomics for Luminal A Breast Cancer.Cancer medicine · 2024Article
- A Multi-Omics Study of Epigenetic Changes in Type II Alveolar Cells of A/J Mice Exposed to Environmental Tobacco Smoke.International journal of molecular sciences · 2024Article
- Bioinformatic Investigation of Genetic Changes in Paraoxonase Genes in Breast Cancer and Breast Cancer Subtypes.European journal of breast health · 2024Article
- Construction of diagnostic and prognostic models based on gene signatures of nasopharyngeal carcinoma by machine learning methods.Translational cancer research · 2023Article
- LINE-1 promotes tumorigenicity and exacerbates tumor progression via stimulating metabolism reprogramming in non-small cell lung cancer.Molecular cancer · 2022Article
- A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Insights into the role of paraoxonase 2 in human pathophysiology.Journal of biosciences · 2022Article
- Article
- Evidence of Paraoxonases 1, 2, and 3 Expression in Human Ovarian Granulosa Cells.Antioxidants (Basel, Switzerland) · 2021Article
- Article
- The Emerging Roles of Antioxidant Enzymes by Dietary Phytochemicals in Vascular Diseases.Life (Basel, Switzerland) · 2021Review
- The impact of reactive oxygen species in the development of cardiometabolic disorders: a review.Lipids in health and disease · 2021Review
- Paraoxonase-1 and -3 Protein Expression in the Brain of the Tg2576 Mouse Model of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
To achieve malignancy, cancer cells convert numerous signaling pathways, with evasion from cell death being a characteristic hallmark. The cell death machinery represents an anti-cancer target demanding constant identification of tumor-specific signaling molecules. Control of mitochondrial radical formation, particularly superoxide interconnects cell death signals with appropriate mechanistic execution. Superoxide is potentially damaging, but also triggers mitochondrial cytochrome c release. While paraoxonase (PON) enzymes are known to protect against cardiovascular diseases, recent data revealed that PON2 attenuated mitochondrial radical formation and execution of cell death. Another family member, PON3, is poorly investigated. Using various cell culture systems and knockout mice, here we addressed its potential role in cancer. PON3 is found overexpressed in various human tumors and diminishes mitochondrial superoxide formation. It directly interacts with coenzyme Q10 and presumably acts by sequestering ubisemiquinone, leading to enhanced cell death resistance. Localized to the endoplasmic reticulum (ER) and mitochondria, PON3 abrogates apoptosis in response to DNA damage or intrinsic but not extrinsic stimulation. Moreover, PON3 impaired ER stress-induced apoptotic MAPK signaling and CHOP induction. Therefore, our study reveals the mechanism underlying PON3's anti-oxidative effect and demonstrates a previously unanticipated function in tumor cell development. We suggest PONs represent a novel class of enzymes crucially controlling mitochondrial radical generation and cell death.
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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.