ArticleCell cycle (Georgetown, Tex.)2012
Hereditary ovarian cancer and two-compartment tumor metabolism: epithelial loss of BRCA1 induces hydrogen peroxide production, driving oxidative stress and NFκB activation in the tumor stroma.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
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- Redox-Responsive Polymeric Nanoparticle for Nucleic Acid Delivery and Cancer Therapy: Progress, Opportunities, and Challenges.Macromolecular bioscience · 2024Review
- Does each Component of Reactive Oxygen Species have a Dual Role in the Tumor Microenvironment?Current medicinal chemistry · 2024Review
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- Recent Advances in Electrochemical Sensing of Hydrogen Peroxide (HNanomaterials (Basel, Switzerland) · 2022Review
- NF-κB Signaling in Tumor Pathways Focusing on Breast and Ovarian Cancer.Oncology reviews · 2022Review
- Monocarboxylate Transporter 4 in Cancer-Associated Fibroblasts Is a Driver of Aggressiveness in Aerodigestive Tract Cancers.Frontiers in oncology · 2022Article
- Effects of Silver Nanoparticles and Silver Nitrate on mRNA and microRNA Expression in Human Hepatocellular Carcinoma Cells (HepG2).Journal of nanoscience and nanotechnology · 2021Article
- Possible Beneficial Effects of N-Acetylcysteine for Treatment of Triple-Negative Breast Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- Article
- Interplay Between MicroRNAs and Oxidative Stress in Ovarian Conditions with a Focus on Ovarian Cancer and Endometriosis.International journal of molecular sciences · 2019Review
- PML-Regulated Mitochondrial Metabolism Enhances Chemosensitivity in Human Ovarian Cancers.Cell metabolism · 2019Article
- GPX2 suppression of HOncoTargets and therapy · 2019Article
- The metabolic cross-talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role.Medicinal research reviews · 2018Review
- MiR-21-mediated Metabolic Alteration of Cancer-associated Fibroblasts and Its Effect on Pancreatic Cancer Cell Behavior.International journal of biological sciences · 2018Article
- Cancer-associated fibroblasts enhance pancreatic cancer cell invasion by remodeling the metabolic conversion mechanism.Oncology reports · 2017Article
- Parkin and mitophagy in cancer.Oncogene · 2017Review
- Autophagy protects ovarian cancer-associated fibroblasts against oxidative stress.Cell cycle (Georgetown, Tex.) · 2016Article
- Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the BRCA1 tumor suppressor gene are commonly found in hereditary ovarian cancers. Here, we used a co-culture approach to study the metabolic effects of BRCA1-null ovarian cancer cells on adjacent tumor-associated stromal fibroblasts. Our results directly show that BRCA1-null ovarian cancer cells produce large amounts of hydrogen peroxide, which can be abolished either by administration of simple antioxidants (N-acetyl-cysteine; NAC) or by replacement of the BRCA1 gene. Thus, the BRCA1 gene normally suppresses tumor growth by functioning as an antioxidant. Importantly, hydrogen peroxide produced by BRCA1-null ovarian cancer cells induces oxidative stress and catabolic processes in adjacent stromal fibroblasts, such as autophagy, mitophagy and glycolysis, via stromal NFκB activation. Catabolism in stromal fibroblasts was also accompanied by the upregulation of MCT4 and a loss of Cav-1 expression, which are established markers of a lethal tumor microenvironment. In summary, loss of the BRCA1 tumor suppressor gene induces hydrogen peroxide production, which then leads to metabolic reprogramming of the tumor stroma, driving stromal-epithelial metabolic coupling. Our results suggest that new cancer prevention trials with antioxidants are clearly warranted in patients that harbor hereditary/familial BRCA1 mutations.
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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.