ArticlePLoS biology2023
FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 21 citations in OpenAlex.
- Kaempferol inhibited pyroptosis in preeclampsia by modulating the NLRP3 inflammasome through the STAT3-associated mitophagy pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- FBXO3-mediated DUSP9 ubiquitination promotes leukemia stem cell maintenance and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Cell reports. Medicine · 2026Article
- ACSL4 Inhibition by AS-252424 Protects Visual Function by Suppressing RGC Ferroptosis After Retinal Ischemia Reperfusion Injury.Molecular neurobiology · 2026Article
- Targeted inhibition of FBXL2 confers susceptibility of HER2-negative breast cancer to trastuzumab deruxtecan.Nature cancer · 2026Article
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- CircLRBA Promotes Epithelial-Mesenchymal Transition, Immune Evasion, Chemoimmunotherapy Resistance and Metastasis Through Stabilizing Twist1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrated multi-omics analysis identifies key biomarkers associated with post-translational modifications and RNA methylation in clear cell renal cell carcinoma.Discover oncology · 2025Article
- ATF2-mediated Transcriptional Activation of USP4 Stabilizes KMT2A Protein and Promotes Trophoblast Dysfunction.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Article
- Intervention of machine learning in bladder cancer research using multi-omics datasets: systematic review on biomarker identification.Discover oncology · 2025Review
- Twist1 Regulates the Immune Checkpoint VISTA and Promotes the Proliferation, Migration and Progression of Pancreatic Cancer Cells.Journal of cellular and molecular medicine · 2025Article
- USP4 promotes proliferation and metastasis in human lung adenocarcinoma.Scientific reports · 2025Article
- The Deubiquitinating Enzyme USP4 Promotes Trophoblast Dysfunction by Stabilizing RYBP.Cell biochemistry and biophysics · 2025Article
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Distinct Regions within SAP25 Recruit O-Linked Glycosylation, DNA Demethylation, and Ubiquitin Ligase and Hydrolase Activities to the Sin3/HDAC Complex.Journal of proteome research · 2024Article
- Fbxo45 facilitates the malignant progression of breast cancer by targeting Bim for ubiquitination and degradation.BMC cancer · 2024Article
- Updated insights into the NLRP3 inflammasome in postoperative cognitive dysfunction: emerging mechanisms and treatments.Frontiers in aging neuroscience · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor metastasis is the major cause of breast cancer morbidity and mortality. It has been reported that the F-box protein FBXO3 functions as an E3 ubiquitin ligase in regulating various biological processes, including host autoimmune, antiviral innate immunity, and inflammatory response. However, the role of FBXO3 in tumor metastasis remains elusive. We have previously shown that ΔNp63α is a common inhibitory target in oncogene-induced cell motility and tumor metastasis. In this study, we show that FBXO3 plays a vital role in PI3K-mediated breast cancer metastasis independent of its E3 ligase activity and ΔNp63α in breast cancer cells and in mouse. FBXO3 can bind to and stabilize USP4, leading to Twist1 protein stabilization and increased breast cancer cell migration and tumor metastasis. Mechanistically, FBXO3 disrupts the interaction between USP4 and aspartyl aminopeptidase (DNPEP), thereby protecting USP4 from DNPEP-mediated degradation. Furthermore, p110αH1047R facilitates the phosphorylation and stabilization of FBXO3 in an ERK1-dependent manner. Knockdown of either FBXO3 or USP4 leads to significant inhibition of PI3K-induced breast cancer metastasis. Clinically, elevated expression of p110α/FBXO3/USP4/Twist1 is associated with poor overall survival (OS) and recurrence-free survival (RFS) of breast cancer patients. Taken together, this study reveals that the FBXO3-USP4-Twist1 axis is pivotal in PI3K-mediated breast tumor metastasis and that FBXO3/USP4 may be potential therapeutic targets for breast cancer treatment.
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.