ArticleMolecular cancer research : MCR2016
HDAC6 Deacetylates HMGN2 to Regulate Stat5a Activity and Breast Cancer Growth.
Article in Molecular cancer research : MCR, 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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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- The Roles of STAT3 and STAT5 in Breast Cancer.Cancers · 2025Review
- HMGN2 accelerates the proliferation and cell cycle progression of glioblastoma by regulating CDC20 expression.Genes & diseases · 2025Article
- Deficiency of HMGN2 enhances antibacterial activity of macrophages by promoting H3 histone modification-mediated CD14/iNOS expression.Frontiers in immunology · 2025Article
- Dissecting the epigenetic orchestra of HDAC isoforms in breast cancer development: a review.Medical oncology (Northwood, London, England) · 2024Review
- PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- Impact of IL-15 and latency reversing agent combinations in the reactivation and NK cell-mediated suppression of the HIV reservoir.Scientific reports · 2022Article
- MicroRNA-22 represses glioma development via activation of macrophage-mediated innate and adaptive immune responses.Oncogene · 2022Article
- Novel biomarkers predict prognosis and drug-induced neuroendocrine differentiation in patients with prostate cancer.Frontiers in endocrinology · 2022Article
- Analysis of Sociodemographic, Clinical, and Genomic Factors Associated With Breast Cancer Mortality in the Linked Surveillance, Epidemiology, and End Results and Medicare Database.JAMA network open · 2021Article
- Serine residues 726 and 780 have nonredundant roles regulating STAT5a activity in luminal breast cancer.Scientific reports · 2021Article
- A Translational Study of a Silicon Phthalocyanine Substituted with a Histone Deacetylase Inhibitor for Photodynamic Therapy.ACS omega · 2020Article
- Critical review of non-histone human substrates of metal-dependent lysine deacetylases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Review
- Exogenous HMGN2 inhibits the migration and invasion of osteosarcoma cell lines.Translational cancer research · 2020Article
- Review
- Biological Functions of HMGN Chromosomal Proteins.International journal of molecular sciences · 2020Review
- Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.Science translational medicine · 2019Article
- HDACs control RUNX2 expression in cancer cells through redundant and cell context-dependent mechanisms.Journal of experimental & clinical cancer research : CR · 2019Article
- Protective Effect of Tubastatin A in CLP-Induced Lethal Sepsis.Inflammation · 2018Article
- Identification of human age-associated gene co-expressions in functional modules using liquid association.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Stat5a is a transcription factor utilized by several cytokine/hormone receptor signaling pathways that promotes transcription of genes associated with proliferation, differentiation, and survival of cancer cells. However, there are currently no clinically approved therapies that directly target Stat5a, despite ample evidence that it contributes to breast cancer pathogenesis. Here, deacetylation of the Stat5a coactivator and chromatin-remodeling protein HMGN2 on lysine residue K2 by HDAC6 promotes Stat5a-mediated transcription and breast cancer growth. HDAC6 inhibition both in vitro and in vivo enhances HMGN2 acetylation with a concomitant reduction in Stat5a-mediated signaling, resulting in an inhibition of breast cancer growth. Furthermore, HMGN2 is highly acetylated at K2 in normal human breast tissue, but is deacetylated in primary breast tumors and lymph node metastases, suggesting that targeting HMGN2 deacetylation is a viable treatment for breast cancer. Together, these results reveal a novel mechanism by which HDAC6 activity promotes the transcription of Stat5a target genes and demonstrate utility of HDAC6 inhibition for breast cancer therapy. IMPLICATIONS: HMGN2 deacetylation enhances Stat5a transcriptional activity, thereby regulating prolactin-induced gene transcription and breast cancer growth. Mol Cancer Res; 14(10); 994-1008. ©2016 AACR.
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