ArticleNature communications2018
Targeting the BRD4/FOXO3a/CDK6 axis sensitizes AKT inhibition in luminal breast cancer.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- CDK4/6 inhibitors versus PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: An updated systematic review and network meta-analysis of 28 randomized controlled trials.Frontiers in oncology · 2022Pooled it
- BRD4 inhibition mitigates acute and chronic corneal injury following topical nitrogen mustard exposure.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Article
- The future of Forkhead box O transcription factors.The Biochemical journal · 2026Review
- BET Bromodomain Inhibition Reverses CDK4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer via Induction of miR-34a-5p.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Super-enhancer profiling reveals ThPOK/ZBTB7B, a CD4Cellular and molecular life sciences : CMLS · 2025Article
- Establishment of a patient-derived drug-resistant oral squamous cell carcinoma animal model.Animal models and experimental medicine · 2025Article
- P300-dependent acetylation of the FOXQ1 complex activates super-enhancers to promote colorectal cancer proliferation and metastasis.Communications biology · 2025Article
- Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway.Journal of translational medicine · 2025Article
- Advancing brain tumor therapy: unveiling the potential of PROTACs for targeted protein degradation.Cytotechnology · 2025Review
- Article
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Helicobacter Pylori-induced BRD2 mInternational journal of biological sciences · 2025Article
- Emergent properties of the lysine methylome reveal regulatory roles via protein interactions and histone mimicry.Epigenomics · 2025Article
- The Roles of Forkhead Box O3a (FOXO3a) in Bone and Cartilage Diseases - A Narrative Review.Drug design, development and therapy · 2025Review
- A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance.Oncogene · 2024Review
- FOXO3a-interacting proteins' involvement in cancer: a review.Molecular biology reports · 2024Review
- FOXO transcription factors as mediators of stress adaptation.Nature reviews. Molecular cell biology · 2024Review
- Role and regulation of FOXO3a: new insights into breast cancer therapy.Frontiers in pharmacology · 2024Review
- Targeting AKT induced Ferroptosis through FTO/YTHDF2-dependent GPX4 m6A methylation up-regulating and degradating in colorectal cancer.Cell death discovery · 2023Article
5 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
21 authors at 7 institutions in 2 countries.
Funding
Abstract
BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or CDK6 significantly overcomes the resistance of luminal breast cancer cells to AKT inhibitors in vitro and in vivo. Our study reports the involvement of BRD4/FOXO3a/CDK6 axis in AKTi resistance and provides potential therapeutic strategies for treating resistant 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.