ArticleThe Journal of biological chemistry2013
Loss of epigenetic Kruppel-like factor 4 histone deacetylase (KLF-4-HDAC)-mediated transcriptional suppression is crucial in increasing vascular endothelial growth factor (VEGF) expression in breast cancer.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Synthesis of 2-Aryl(alkyl)benzimidazole Hydroxamic Acids as HDAC Inhibitors with Anti-Angiogenesis Properties.ChemMedChem · 2026Article
- Targeting the NAT10-HDAC4 positive feedback loop counteracts immunosuppression in breast cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- The role of pluripotency regulators in triple-negative breast cancer immune response.Frontiers in genetics · 2026Review
- Histone acetylation modulators in breast cancer.Breast cancer research : BCR · 2025Review
- Mechanisms of HDACs in cancer development.Frontiers in immunology · 2025Review
- Unlocking the epigenetic code: new insights into triple-negative breast cancer.Frontiers in oncology · 2024Review
- A novel GRK3-HDAC2 regulatory pathway is a key direct link between neuroendocrine differentiation and angiogenesis in prostate cancer progression.Cancer letters · 2023Article
- Update on histone deacetylase inhibitors in peripheral T-cell lymphoma (PTCL).Clinical epigenetics · 2023Review
- Krüppel-like factors in tumors: Key regulators and therapeutic avenues.Frontiers in oncology · 2023Review
- CREPT Disarms the Inhibitory Activity of HDAC1 on Oncogene Expression to Promote Tumorigenesis.Cancers · 2022Article
- Epigenetics and environment in breast cancer: New paradigms for anti-cancer therapies.Frontiers in oncology · 2022Review
- LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through SuppressingFrontiers in cell and developmental biology · 2021Article
- Targeting Histone Modifications in Breast Cancer: A Precise Weapon on the Way.Frontiers in cell and developmental biology · 2021Review
- [Quantitative proteomics and bioinformatics analyses of human coronary artery endothelial cell injury induced by Kawasaki disease].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2020Article
- Understanding Failure and Improving Treatment Using HDAC Inhibitors for Prostate Cancer.Biomedicines · 2020Review
- Unravelling Structure, Localization, and Genetic Crosstalk of KLF3 in Human Breast Cancer.BioMed research international · 2020Article
- Identification of placental genes linked to selective intrauterine growth restriction (IUGR) in dichorionic twin pregnancies: gene expression profiling study.Human genetics · 2019Article
- Article
- Atheroprotective Flow Upregulates ITPR3 (Inositol 1,4,5-Trisphosphate Receptor 3) in Vascular Endothelium via KLF4 (Krüppel-Like Factor 4)-Mediated Histone Modifications.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Induction of cell cycle arrest and inflammatory genes by combined treatment with epigenetic, differentiating, and chemotherapeutic agents in triple-negative breast cancer.Breast cancer research : BCR · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor (VEGF) is recognized as an important angiogenic factor that promotes angiogenesis in a series of pathological conditions, including cancer, inflammation, and ischemic disorders. We have recently shown that the inflammatory transcription factor SAF-1 is, at least in part, responsible for the marked increase of VEGF levels in breast cancer. Here, we show that SAF-1-mediated induction of VEGF is repressed by KLF-4 transcription factor. KLF-4 is abundantly present in normal breast epithelial cells, but its level is considerably reduced in breast cancer cells and clinical cancer tissues. In the human VEGF promoter, SAF-1- and KLF-4-binding elements are overlapping, whereas SAF-1 induces and KLF-4 suppresses VEGF expression. Ectopic overexpression of KLF-4 and RNAi-mediated inhibition of endogenous KLF-4 supported the role of KLF-4 as a transcriptional repressor of VEGF and an inhibitor of angiogenesis in breast cancer cells. We show that KLF-4 recruits histone deacetylases (HDACs) -2 and -3 at the VEGF promoter. Chronological ChIP assays demonstrated the occupancy of KLF-4, HDAC2, and HDAC3 in the VEGF promoter in normal MCF-10A cells but not in MDA-MB-231 cancer cells. Co-transfection of KLF-4 and HDAC expression plasmids in breast cancer cells results in synergistic repression of VEGF expression and inhibition of angiogenic potential of these carcinoma cells. Together these results identify a new mechanism of VEGF up-regulation in cancer that involves concomitant loss of KLF-4-HDAC-mediated transcriptional repression and active recruitment of SAF-1-mediated transcriptional activation.
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