ArticleOncogene2016
FOXC1 is involved in ERα silencing by counteracting GATA3 binding and is implicated in endocrine resistance.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 41 citations in OpenAlex.
- Treatment and prognosis of patients with hormone receptor-low positive (1%-10%) breast cancer: a retrospective propensity score-matched analysis.Breast cancer (Tokyo, Japan) · 2025Article
- The Role of the Fox Gene in Breast Cancer Progression.International journal of molecular sciences · 2025Review
- Article
- Reciprocal regulation of forkhead box C1 and L1 cell adhesion molecule contributes to triple-negative breast cancer progression.Breast cancer research and treatment · 2024Article
- Epigenetic Profiles of Triple-Negative Breast Cancers of African American and White Females.JAMA network open · 2023Article
- Role of Fork-Head Box Genes in Breast Cancer: From Drug Resistance to Therapeutic Targets.Biomedicines · 2023Review
- Survival is associated with repressive histone trimethylation markers in both HR-positive HER2-negative and triple-negative breast cancer patients.Virchows Archiv : an international journal of pathology · 2023Article
- Stilbenes: a promising small molecule modulator for epigenetic regulation in human diseases.Frontiers in pharmacology · 2023Review
- Review
- Functional and regulatory aspects of oxidative stress response in X monosomy.In vitro cellular & developmental biology. Animal · 2021Article
- CUL4B Promotes Breast Carcinogenesis by Coordinating with Transcriptional Repressor Complexes in Response to Hypoxia Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Therapeutically Targeting Cancers That Overexpress FOXC1: A Transcriptional Driver of Cell Plasticity, Partial EMT, and Cancer Metastasis.Frontiers in oncology · 2021Review
- Forkhead box C1 promotes metastasis and invasion of non-small cell lung cancer by binding directly to the lysyl oxidase promoter.Cancer science · 2019Article
- MUC1-C Activates the NuRD Complex to Drive Dedifferentiation of Triple-Negative Breast Cancer Cells.Cancer research · 2019Article
- The Diverse Consequences ofCancers · 2019Review
- The Dominant Role of Forkhead Box Proteins in Cancer.International journal of molecular sciences · 2018Review
- FOXC1 induces cancer stem cell-like properties through upregulation of beta-catenin in NSCLC.Journal of experimental & clinical cancer research : CR · 2018Article
- Targeting EZH2 reactivates a breast cancer subtype-specific anti-metastatic transcriptional program.Nature communications · 2018Article
- Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data.Nature communications · 2018Article
- FOXC1 in cancer development and therapy: deciphering its emerging and divergent roles.Therapeutic advances in medical oncology · 2017Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Estrogen receptor-α (ERα) mediates the essential biological function of estrogen in breast development and tumorigenesis. Multiple mechanisms, including pioneer factors, coregulators and epigenetic modifications have been identified as regulators of ERα signaling in breast cancer. However, previous studies of ERα regulation have focused on luminal and HER2-positive subtypes rather than basal-like breast cancer (BLBC), in which ERα is underexpressed. In addition, mechanisms that account for the decrease or loss of ER expression in recurrent tumors after endocrine therapy remain elusive. Here, we demonstrate a novel FOXC1-driven mechanism that suppresses ERα expression in breast cancer. We find that FOXC1 competes with GATA-binding protein 3 (GATA3) for the same binding regions in the cis-regulatory elements upstream of the ERα gene and thereby downregulates ERα expression and consequently its transcriptional activity. The forkhead domain of FOXC1 is essential for the competition with GATA3 for DNA binding. Counteracting the action of GATA3 at the ERα promoter region, overexpression of FOXC1 hinders recruitment of RNA polymerase II and increases histone H3K9 trimethylation at ERα promoters. Importantly, ectopic FOXC1 expression in luminal breast cancer cells reduces sensitivity to estrogen and tamoxifen. Furthermore, in breast cancer patients with ER-positive primary tumors who received adjuvant tamoxifen treatment, FOXC1 expression is associated with decreased or undetectable ER expression in recurrent tumors. Our findings highlight a clinically relevant mechanism that contributes to the low or absent ERα expression in BLBC. This study suggests a new paradigm to study ERα regulation during breast cancer progression and indicates a role of FOXC1 in the modulation of cellular response to endocrine treatment.
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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.