ArticleNucleic acids research2022
Estrogen regulates divergent transcriptional and epigenetic cell states in breast cancer.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 23 citations in OpenAlex.
- Integrative pipeline to profile and target endocrine therapy-insensitive cell populations in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Systematic comparison of estimates of transcription factor activity by ATAC-seq and multiplexed reporter assays.Molecular systems biology · 2026Article
- Robust and generalizable CNV detection for single-cell sequencing assays.Nucleic acids research · 2026Article
- Serial Spatial Transcriptomics Reveal Divergent Routes to Therapy Resistance in Metastatic Breast Cancer.Research square · 2026Article
- Layered Single-Cell Heterogeneity in Hormone Receptor Signaling Across Mouse Organoids and Human ERα+ Cancer Cells.bioRxiv : the preprint server for biology · 2026Article
- Molecular subtype-specific breast cancer organoids: development of an FGF-free estradiol valerate culture system for precision drug screening.Cancer cell international · 2026Article
- H3K27me3 chromatin heterogeneity reveals variable cell responses to estrogen and endocrine treatment.bioRxiv : the preprint server for biology · 2025Article
- Interpretable and integrative analysis of single-cell multiomics with scMKL.Communications biology · 2025Article
- Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A Snapshot of the Role of Estrogen-Regulated Divergent Non-Coding Transcripts.Clinical and translational discovery · 2025Article
- Mechanisms and Therapeutic Strategies for Endocrine Resistance in Breast Cancer: A Comprehensive Review and Meta-Analysis.Cancers · 2025Review
- Single-Cell Analyses Reveal a Functionally Heterogeneous Exhausted CD8+ T-cell Subpopulation That Is Correlated with Response to Checkpoint Therapy in Melanoma.Cancer research · 2025Article
- Response Gene to Complement 32 promotes cell proliferation and tamoxifen resistance in breast cancer via elevated FoxM1 expression.PloS one · 2025Article
- Review
- Selective Estrogen Receptor Modulators' (SERMs) Influence onInternational journal of molecular sciences · 2024Article
- Correlation between the RNA Expression and the DNA Methylation of Estrogen Receptor Genes in Normal and Malignant Human Tissues.Current issues in molecular biology · 2024Article
- Extracellular Matrix Cues Regulate Mechanosensing and Mechanotransduction of Cancer Cells.Cells · 2024Review
- Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer.Frontiers in oncology · 2024Review
- Transcriptional state dynamics lead to heterogeneity and adaptive tumor evolution in urothelial bladder carcinoma.Communications biology · 2023Article
- Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Breast cancers are known to be driven by the transcription factor estrogen receptor and its ligand estrogen. While the receptor's cis-binding elements are known to vary between tumors, heterogeneity of hormone signaling at a single-cell level is unknown. In this study, we systematically tracked estrogen response across time at a single-cell level in multiple cell line and organoid models. To accurately model these changes, we developed a computational tool (TITAN) that quantifies signaling gradients in single-cell datasets. Using this approach, we found that gene expression response to estrogen is non-uniform, with distinct cell groups expressing divergent transcriptional networks. Pathway analysis suggested the two most distinct signatures are driven separately by ER and FOXM1. We observed that FOXM1 was indeed activated by phosphorylation upon estrogen stimulation and silencing of FOXM1 attenuated the relevant gene signature. Analysis of scRNA-seq data from patient samples confirmed the existence of these divergent cell groups, with the FOXM1 signature predominantly found in ER negative cells. Further, multi-omic single-cell experiments indicated that the different cell groups have distinct chromatin accessibility states. Our results provide a comprehensive insight into ER biology at the single-cell level and potential therapeutic strategies to mitigate resistance to therapy.
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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.