ArticleMolecular cancer therapeutics2008
Reprogramming epigenetic silencing: artificial transcription factors synergize with chromatin remodeling drugs to reactivate the tumor suppressor mammary serine protease inhibitor.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 62 citations in OpenAlex.
- Integrating the tumor-suppressive activity of Maspin with p53 in retuning the epithelial homeostasis: A working hypothesis and applicable prospects.Frontiers in oncology · 2022Review
- Reprogramming the anti-tumor immune response via CRISPR genetic and epigenetic editing.Molecular therapy. Methods & clinical development · 2021Review
- Hypermethylation ofFrontiers in cell and developmental biology · 2021Article
- Epigenome engineering: new technologies for precision medicine.Nucleic acids research · 2020Article
- Inhibiting histone deacetylases suppresses glucose metabolism and hepatocellular carcinoma growth by restoring FBP1 expression.Scientific reports · 2017Article
- Waking up dormant tumor suppressor genes with zinc fingers, TALEs and the CRISPR/dCas9 system.Oncotarget · 2016Article
- Writing of H3K4Me3 overcomes epigenetic silencing in a sustained but context-dependent manner.Nature communications · 2016Article
- Epigenetic Editing: On the Verge of Reprogramming Gene Expression at Will.Current genetic medicine reports · 2016Review
- Epigenome engineering in cancer: fairytale or a realistic path to the clinic?Frontiers in oncology · 2015Review
- Prolonged re-expression of the hypermethylated gene EPB41L3 using artificial transcription factors and epigenetic drugs.Epigenetics · 2015Article
- Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers.The Biochemical journal · 2014Review
- Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation.Nucleic acids research · 2014Article
- A Potential New Therapeutic Approach for Friedreich Ataxia: Induction of Frataxin Expression With TALE Proteins.Molecular therapy. Nucleic acids · 2013Article
- Functional validation of putative tumor suppressor gene C13ORF18 in cervical cancer by Artificial Transcription Factors.Molecular oncology · 2013Article
- Role of maspin in cancer.Clinical and translational medicine · 2013Article
- Writing and rewriting the epigenetic code of cancer cells: from engineered proteins to small molecules.Molecular pharmacology · 2013Review
- Breaking through an epigenetic wall: re-activation of Oct4 by KRAB-containing designer zinc finger transcription factors.Epigenetics · 2013Article
- The p16-specific reactivation and inhibition of cell migration through demethylation of CpG islands by engineered transcription factors.Human gene therapy · 2012Article
- Targeting serous epithelial ovarian cancer with designer zinc finger transcription factors.The Journal of biological chemistry · 2012Article
- Snail transcription factor negatively regulates maspin tumor suppressor in human prostate cancer cells.BMC cancer · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Mammary serine protease inhibitor (maspin) is an important tumor suppressor gene whose expression is associated not only with tumor growth inhibition but also with decreased angiogenesis and metastasis. Maspin expression is down-regulated in metastatic tumors by epigenetic mechanisms, including aberrant promoter hypermethylation. We have constructed artificial transcription factors (ATFs) as novel therapeutic effectors able to bind 18-bp sites in the maspin promoter and reactivate maspin expression in cell lines that harbor an epigenetically silenced promoter. In this article, we have investigated the influence of epigenetic modifications on ATF-mediated regulation of maspin by challenging MDA-MB-231 breast cancer cells, comprising a methylated maspin promoter, with different doses of ATFs and chromatin remodeling drugs: the methyltransferase inhibitor 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor suberoylanilide hydroxamic acid. We found that the ATFs synergized with both inhibitors in reactivating endogenous maspin expression. The strongest synergy was observed with the triple treatment ATF-126 + 5-aza-2'-deoxycytidine + suberoylanilide hydroxamic acid, in which the tumor suppressor was reactivated by 600-fold. Furthermore, this combination inhibited tumor cell proliferation by 95%. Our data suggest that ATFs enhance the efficiency of chromatin remodeling drugs in reactivating silenced tumor suppressors. Our results document the power of a novel therapeutic approach that combines both epigenetic and genetic (sequence-specific ATFs) strategies to reactivate specifically silenced regions of the genome and reprogram cellular phenotypes.
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.