ArticleScience advances2019
Inhibition of histone methyltransferase DOT1L silences ERα gene and blocks proliferation of antiestrogen-resistant breast cancer cells.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 91 citations in OpenAlex.
- Review
- Targeting DOT1L Reactivates HERV-K to Drive Cell-Autonomous and Paracrine Senescence in Adenocarcinoma of the Esophagogastric Junction.Cancer research · 2026Article
- Identification of LncRNAs scaffolding a chromatin-associated gene regulatory complex in breast cancer cells comprising ERα, DOT1L and menin.Cell communication and signaling : CCS · 2026Article
- DOT1L inhibition exerts the anti-tumor effect by activating interferon signaling in breast cancer cells.Clinical epigenetics · 2025Article
- DOT1L as a Therapeutic Target: Insights into Epigenetic Regulation and Cancer Treatment.Biomolecules & therapeutics · 2025Review
- 5'-Methylthioadenosine Metabolic Reprogramming Drives H3K79 Monomethylation-Mediated PAK2 Upregulation to Promote Cadmium-Induced Breast Cancer Progression by Impairing Autophagic Flux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Epigenetic Regulation of Immune Responses in Endocrine-Related Cancers and Its Role in Immunotherapy.Cancers · 2025Review
- Multi-omics based and AI-driven drug repositioning for epigenetic therapy in female malignancies.Journal of translational medicine · 2025Review
- Discovery of the first-in-class DOT1L PROTAC degrader.European journal of medicinal chemistry · 2025Article
- DOT1L Mediates Stem Cell Maintenance and Represents a Therapeutic Vulnerability in Cancer.Cancer research · 2025Review
- LncRNA PVT1 links estrogen receptor alpha and the polycomb repressive complex 2 in suppression of pro-apoptotic genes in hormone-responsive breast cancer.Cell death & disease · 2025Article
- Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Article
- DOT1L protects against podocyte injury in diabetic kidney disease through phospholipase C-like 1.Cell communication and signaling : CCS · 2024Article
- Essential gene screening identifies the bromodomain-containing protein BRPF1 as a new actionable target for endocrine therapy-resistant breast cancers.Molecular cancer · 2024Article
- Discovery of first-in-class DOT1L inhibitors against the R231Q gain-of-function mutation in the catalytic domain with therapeutic potential of lung cancer.Acta pharmaceutica Sinica. B · 2024Article
- Beyond the Usual Suspects: Examining the Role of Understudied Histone Variants in Breast Cancer.International journal of molecular sciences · 2024Review
- Epigenetic regulation of breast cancer metastasis.Cancer metastasis reviews · 2024Review
- The emerging role of DOT1L in cell proliferation and differentiation: Friend or foe.Histology and histopathology · 2024Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer (BC) resistance to endocrine therapy results from constitutively active or aberrant estrogen receptor α (ERα) signaling, and ways to block ERα pathway in these tumors are sought after. We identified the H3K79 methyltransferase DOT1L as a novel cofactor of ERα in BC cell chromatin, where the two proteins colocalize to regulate estrogen target gene transcription. DOT1L blockade reduces proliferation of hormone-responsive BC cells in vivo and in vitro, consequent to cell cycle arrest and apoptotic cell death, with widespread effects on ER-dependent gene transcription, including ERα and FOXA1 gene silencing. Antiestrogen-resistant BC cells respond to DOT1L inhibition also in mouse xenografts, with reduction in ERα levels, H3K79 methylation, and tumor growth. These results indicate that DOT1L is an exploitable epigenetic target for treatment of endocrine therapy-resistant ERα-positive BCs.
Indexed as
Identifiers
What OpenQuestion holds
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.