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- W4384665611 abstract "Scientists have used pharmacological inhibitors of polycomb proteins to restore the expression of tumor suppressor genes and stop cancer proliferation and invasion. A major limitation of this approach is that key transcriptional activators, such as TP53 and BAF SWI/SNF, are often mutated in cancer. Poor clinical results for polycomb-targeting therapies in solid cancers, including triple-negative breast cancer (TNBC), could discourage the further development of epigenetic monotherapies. Here, we performed epigenome actuation with a synthetic reader-actuator (SRA) that binds trimethylated histone H3 lysine 27 in polycomb chromatin and modulates core transcriptional activators. In SRA-expressing TNBC BT-549 cells, 122 genes become upregulated ≥2-fold, including the genes involved in cell death, cell cycle arrest, and migration inhibition. The SRA-expressing spheroids showed reduced size in Matrigel and loss of invasion. Therefore, targeting Mediator-recruiting regulators to silenced chromatin can activate tumor suppressors and stimulate anti-cancer phenotypes, and further development of robust gene regulators might benefit TNBC patients." @default.
- W4384665611 created "2023-07-20" @default.
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- W4384665611 date "2023-08-01" @default.
- W4384665611 modified "2023-09-26" @default.
- W4384665611 title "Synthetic Reader-Actuators Targeted to Polycomb-Silenced Genes Block Triple-Negative Breast Cancer Proliferation and Invasion" @default.
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- W4384665611 doi "https://doi.org/10.1089/genbio.2023.0020" @default.
- W4384665611 hasPublicationYear "2023" @default.
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