ArticleThe Journal of clinical investigation2017
Geminin facilitates FoxO3 deacetylation to promote breast cancer cell metastasis.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- Dual inhibition of glycolysis and glutaminolysis by targeting FOXO3 for hepatocellular carcinoma treatment.Oncogene · 2026Article
- A Vascular Invasion-Related Gene Signature Identifies NUP35 as a Driver of Angiogenesis and Poor Prognosis in Pancreatic Ductal Adenocarcinoma.Biomedicines · 2026Article
- Reversible acetylation of Hpo regulates the Hippo pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Role of the Fox Gene in Breast Cancer Progression.International journal of molecular sciences · 2025Review
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Differentially localized protein identification for breast cancer based on deep learning in immunohistochemical images.Communications biology · 2024Article
- Forkhead box O proteins: steering the course of stem cell fate.Cell regeneration (London, England) · 2024Review
- Article
- HDAC3 and HDAC8 PROTAC dual degrader reveals roles of histone acetylation in gene regulation.Cell chemical biology · 2023Article
- Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer.Pharmaceutics · 2023Review
- HPV16E1 downregulation altered the cell characteristics involved in cervical cancer development.Scientific reports · 2023Article
- HDAC3 Inhibition Promotes Antitumor Immunity by Enhancing CXCL10-Mediated Chemotaxis and Recruiting of Immune Cells.Cancer immunology research · 2023Article
- The FOXO1 inhibitor AS1842856 triggers apoptosis in glioblastoma multiforme and basal-like breast cancer cells.FEBS open bio · 2023Article
- The Pan-Cancer Multi-Omics Landscape of FOXO Family Relevant to Clinical Outcome and Drug Resistance.International journal of molecular sciences · 2022Article
- METTL3 acetylation impedes cancer metastasis via fine-tuning its nuclear and cytosolic functions.Nature communications · 2022Article
- Prognostic value of HPV 16/18 genotyping and geminin mRNA quantification in low-grade cervical squamous intraepithelial lesion.Bioengineered · 2021Article
- Deacetylation of Transcription Factors in Carcinogenesis.International journal of molecular sciences · 2021Review
- OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Evaluation ofReports of biochemistry & molecular biology · 2021Article
- microRNA-130b-3p Contained in MSC-Derived EVs Promotes Lung Cancer Progression by Regulating the FOXO3/NFE2L2/TXNRD1 Axis.Molecular therapy oncolytics · 2021Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Geminin expression is essential for embryonic development and the maintenance of chromosomal integrity. In spite of this protective role, geminin is also frequently overexpressed in human cancers and the molecular mechanisms underlying its role in tumor progression remain unclear. The histone deacetylase HDAC3 modulates transcription factors to activate or suppress transcription. Little is known about how HDAC3 specifies substrates for modulation among highly homologous transcription factor family members. Here, we have demonstrated that geminin selectively couples the transcription factor forkhead box O3 (FoxO3) to HDAC3, thereby specifically facilitating FoxO3 deacetylation. We determined that geminin-associated HDAC3 deacetylates FoxO3 to block its transcriptional activity, leading to downregulation of the downstream FoxO3 target Dicer, an RNase that suppresses metastasis. Breast cancer cells depleted of geminin or HDAC3 exhibited poor metastatic potential that was attributed to reduced suppression of the FoxO3-Dicer axis. Moreover, elevated levels of geminin, HDAC3, or both together with decreased FoxO3 acetylation and reduced Dicer expression were detected in aggressive human breast cancer specimens. These results underscore a prominent role for geminin in promoting breast cancer metastasis via the enzyme-substrate-coupling mechanism in HDAC3-FoxO3 complex formation.
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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.