ArticleThe Journal of biological chemistry2012
Targeting serous epithelial ovarian cancer with designer zinc finger transcription factors.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD.Frontiers in psychiatry · 2023Article
- Epigenetic Editing in Prostate Cancer: Challenges and Opportunities.Epigenetics · 2022Review
- Lipid nanoparticles for mRNA delivery.Nature reviews. Materials · 2021Review
- Epigenome engineering: new technologies for precision medicine.Nucleic acids research · 2020Article
- The Role of Zinc and Copper in Gynecological Malignancies.Nutrients · 2020Review
- Chromatin engineering offers an opportunity to advance epigenetic cancer therapy.Nature structural & molecular biology · 2019Article
- Activating PTEN Tumor Suppressor Expression with the CRISPR/dCas9 System.Molecular therapy. Nucleic acids · 2019Article
- The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells.BMC systems biology · 2018Article
- Waking up dormant tumor suppressor genes with zinc fingers, TALEs and the CRISPR/dCas9 system.Oncotarget · 2016Article
- Consensus reference gene(s) for gene expression studies in human cancers: end of the tunnel visible?Cellular oncology (Dordrecht, Netherlands) · 2015Review
- Enabling functional genomics with genome engineering.Genome research · 2015Review
- Stable oncogenic silencing in vivo by programmable and targeted de novo DNA methylation in breast cancer.Oncogene · 2015Article
- Prolonged re-expression of the hypermethylated gene EPB41L3 using artificial transcription factors and epigenetic drugs.Epigenetics · 2015Article
- Epigenome engineering in cancer: fairytale or a realistic path to the clinic?Frontiers in oncology · 2015Review
- Specific reactivation of latent HIV-1 with designer zinc-finger transcription factors targeting the HIV-1 5'-LTR promoter.Gene therapy · 2014Article
- Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits β-catenin degradation.Cellular and molecular life sciences : CMLS · 2014Article
- Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation.Nucleic acids research · 2014Article
- Can genome engineering be used to target cancer-associated enhancers?Epigenomics · 2014Review
- Functional validation of putative tumor suppressor gene C13ORF18 in cervical cancer by Artificial Transcription Factors.Molecular oncology · 2013Article
- Writing and rewriting the epigenetic code of cancer cells: from engineered proteins to small molecules.Molecular pharmacology · 2013Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Ovarian cancer is the leading cause of death among gynecological malignancies. It is detected at late stages when the disease is spread through the abdominal cavity in a condition known as peritoneal carcinomatosis. Thus, there is an urgent need to develop novel therapeutic interventions to target advanced stages of ovarian cancer. Mammary serine protease inhibitor (Maspin) represents an important metastasis suppressor initially identified in breast cancer. Herein we have generated a sequence-specific zinc finger artificial transcription factor (ATF) to up-regulate the Maspin promoter in aggressive ovarian cancer cell lines and to interrogate the therapeutic potential of Maspin in ovarian cancer. We found that although Maspin was expressed in some primary ovarian tumors, the promoter was epigenetically silenced in cell lines derived from ascites. Transduction of the ATF in MOVCAR 5009 cells derived from ascitic cultures of a TgMISIIR-TAg mouse model of ovarian cancer resulted in tumor cell growth inhibition, impaired cell invasion, and severe disruption of actin cytoskeleton. Systemic delivery of lipid-protamine-RNA nanoparticles encapsulating a chemically modified ATF mRNA resulted in inhibition of ovarian cancer cell growth in nude mice accompanied with Maspin re-expression in the treated tumors. Gene expression microarrays of ATF-transduced cells revealed an exceptional specificity for the Maspin promoter. These analyses identified novel targets co-regulated with Maspin in human short-term cultures derived from ascites, such as TSPAN12, that could mediate the anti-metastatic phenotype of the ATF. Our work outlined the first targeted, non-viral delivery of ATFs into tumors with potential clinical applications for metastatic ovarian cancers.
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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.