ArticleBreast cancer research : BCR2012
Maintenance of S-nitrosothiol homeostasis plays an important role in growth suppression of estrogen receptor-positive breast tumors.
Article in Breast cancer research : BCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 25 citations in OpenAlex.
- The Role of Oxidative and Nitrosative Stress of Silver Nanoparticles in Human Parasitic Helminth Brugia malayi: A Mechanistic Insight.Acta parasitologica · 2021Article
- Gene Signatures Induced by Ionizing Radiation as Prognostic Tools in an In Vitro Experimental Breast Cancer Model.Cancers · 2021Review
- Nitric oxide-targeted therapy inhibits stemness and increases the efficacy of tamoxifen in estrogen receptor-positive breast cancer cells.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Protein co-expression networks identified from HOT lesions of ER+HER2-Ki-67high luminal breast carcinomas.Scientific reports · 2021Article
- Redox-Dependent Chromatin Remodeling: A New Function of Nitric Oxide as Architect of Chromatin Structure in Plants.Frontiers in plant science · 2019Review
- PCK1 Downregulation Promotes TXNRD1 Expression and Hepatoma Cell Growth via the Nrf2/Keap1 Pathway.Frontiers in oncology · 2018Article
- Thioredoxin promotes survival signaling events under nitrosative/oxidative stress associated with cancer development.Biomedical journal · 2017Review
- TXNRD1 Is an Unfavorable Prognostic Factor for Patients with Hepatocellular Carcinoma.BioMed research international · 2017Article
- Dual targeting of the thioredoxin and glutathione systems in cancer and HIV.The Journal of clinical investigation · 2016Review
- Anti-oxidative stress response genes: bioinformatic analysis of their expression and relevance in multiple cancers.Oncotarget · 2013Article
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10 authors at 2 institutions in 1 country.
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Abstract
introductionProtein denitrosylation by thioredoxin reductase (TrxR) is key for maintaining S-nitrosothiol (SNO) homeostasis, although its role in tumor progression is unknown. Therefore, the present study aimed to assess the role of altered SNO homeostasis in breast cancer cells.
methodsThe impairment of SNO homeostasis in breast cancer cells was achieved with the highly specific TrxR inhibitor auranofin and/or exposure to S-nitroso-L-cysteine. S-nitrosylated proteins were detected using the biotin switch assay. Estrogen receptor (ER) alpha knockdown was achieved using RNA silencing technologies and subcellular localization of ERα was analyzed by confocal microscopy. The Oncomine database was explored for TrxR1 (TXNRD1) expression in breast tumors and TrxR1, ER and p53 expression was analyzed by immunohistochemistry in a panel of breast tumors.
resultsThe impairment of SNO homeostasis enhanced cell proliferation and survival of ER+ MCF-7 cells, but not of MDA-MB-231 (ER-, mut p53) or BT-474 (ER+, mut p53) cells. This enhanced cell growth and survival was associated with Akt, Erk1/2 phosphorylation, and augmented cyclin D1 expression and was abolished by the ER antagonist fulvestrant or the p53 specific inhibitor pifithrin-α. The specific silencing of ERα expression in MCF-7 cells also abrogated the growth effect of TrxR inhibition. Estrogenic deprivation in MCF-7 cells potentiated the pro-proliferative effect of impaired SNO homeostasis. Moreover, the subcellular distribution of ERα was altered, with a predominant nuclear localization associated with phosphorylation at Thr311 in those cells with impaired SNO homeostasis. The impairment of SNO homeostasis also expanded a cancer stem cell-like subpopulation in MCF-7 cells, as indicated by the increase of percentage of CD44+ cells and the augmented capability to form mammospheres in vitro. Notably, ER+ status in breast tumors was significantly associated with lower TXNDR1 mRNA expression and immunohistochemical studies confirmed this association, particularly when p53 abnormalities were absent.
conclusionThe ER status in breast cancer may dictate tumor response to different nitrosative environments. Impairment of SNO homeostasis confers survival advantages to ER+ breast tumors, and these molecular mechanisms may also participate in the development of resistance against hormonal therapies that arise in this type of mammary tumors.
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