ArticleScience signaling2020
Sporadic activation of an oxidative stress-dependent NRF2-p53 signaling network in breast epithelial spheroids and premalignancies.
Article in Science signaling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
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- PCSK5M452I Is a Recessive Hypomorph Exclusive to MCF10DCIS.com Cells.Molecular cancer research : MCR · 2026Article
- Mitochondrial Redox Vulnerabilities in Triple-Negative Breast Cancer: Integrative Perspectives and Emerging Therapeutic Strategies.Metabolites · 2026Review
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- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- Computational modelling identifies primary mediators of crosstalk between DNA damage and oxidative stress responses.PLoS computational biology · 2025Article
- MAPK14/p38α shapes the molecular landscape of endometrial cancer and promotes tumorigenic characteristics.Cell reports · 2025Article
- Fate erasure logic of gene networks underlying direct neuronal conversion of somatic cells by microRNAs.Cell reports · 2025Article
- Proteome-wide copy-number estimation from transcriptomics.Molecular systems biology · 2024Article
- DNA fragility at topologically associated domain boundaries is promoted by alternative DNA secondary structure and topoisomerase II activity.Nucleic acids research · 2024Article
- PALB2-mutated human mammary cells display a broad spectrum of morphological and functional abnormalities induced by increased TGFβ signaling.Cellular and molecular life sciences : CMLS · 2024Article
- Digitize your Biology! Modeling multicellular systems through interpretable cell behavior.bioRxiv : the preprint server for biology · 2023Article
- Nucleocytoplasmic transport of active HER2 causes fractional escape from the DCIS-like state.Nature communications · 2023Article
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- MECHANISTIC AND DATA-DRIVEN MODELS OF CELL SIGNALING: TOOLS FOR FUNDAMENTAL DISCOVERY AND RATIONAL DESIGN OF THERAPY.Current opinion in systems biology · 2021Article
- Metabolic Stress Adaptations Underlie Mammary Gland Morphogenesis and Breast Cancer Progression.Cells · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Breast and mammary epithelial cells experience different local environments during tissue development and tumorigenesis. Microenvironmental heterogeneity gives rise to distinct cell regulatory states whose identity and importance are just beginning to be appreciated. Cellular states diversify when clonal three-dimensional (3D) spheroids are cultured in basement membrane, and one such state is associated with stress tolerance and poor response to anticancer therapeutics. Here, we found that this state was jointly coordinated by the NRF2 and p53 pathways, which were costabilized by spontaneous oxidative stress within 3D cultures. Inhibition of NRF2 or p53 individually disrupted some of the transcripts defining the regulatory state but did not yield a notable phenotype in nontransformed breast epithelial cells. In contrast, combined perturbation prevented 3D growth in an oxidative stress-dependent manner. By integrating systems models of NRF2 and p53 signaling in a single oxidative stress network, we recapitulated these observations and made predictions about oxidative stress profiles during 3D growth. NRF2 and p53 signaling were similarly coordinated in normal breast epithelial tissue and hormone-negative ductal carcinoma in situ lesions but were uncoupled in triple-negative breast cancer (TNBC), a subtype in which p53 is usually mutated. Using the integrated model, we correlated the extent of this uncoupling in TNBC cell lines with the importance of NRF2 in the 3D growth of these cell lines and their predicted handling of oxidative stress. Our results point to an oxidative stress tolerance network that is important for single cells during glandular development and the early stages of breast cancer.
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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.