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- W3139221490 abstract "Steroid receptor coactivator 3 (SRC-3/NCoA3/AIB1), is a key regulator of gene transcription and it plays a central role in breast cancer (BC) tumorigenesis, making it a potential therapeutic target. Beyond its function as an important regulator of estrogen receptor transcriptional activity, SRC-3 also functions as a coactivator for a wide range of other transcription factors, suggesting SRC-3 inhibition can be beneficial in hormone-independent cancers as well. The recent discovery of a potent SRC-3 small molecule inhibitor, SI-2, enabled the further development of additional related compounds. SI-12 is an improved version of SI-2 that like SI-2 has anti-proliferative activity in various cancer types, including BC. Here, we sought to identify gene targets, that when inhibited in the presence of SI-12, would lead to enhanced BC cell cytotoxicity. We performed a genome-scale CRISPR-Cas9 screen in MCF-7 BC cells under conditions of pharmacological pressure with SI-12. A parallel screen was performed with an ER inhibitor, fulvestrant, to shed light on both common and distinct activities between SRC-3 and ERα inhibition. Bearing in mind the key role of SRC-3 in tumorigenesis of other types of cancer, we extended our study by validating potential hits identified from the MCF-7 screen in other cancer cell lines." @default.
- W3139221490 created "2021-03-29" @default.
- W3139221490 creator A5011516096 @default.
- W3139221490 creator A5020634719 @default.
- W3139221490 creator A5021830408 @default.
- W3139221490 creator A5034323622 @default.
- W3139221490 creator A5056985040 @default.
- W3139221490 creator A5057978718 @default.
- W3139221490 creator A5065854386 @default.
- W3139221490 creator A5069521918 @default.
- W3139221490 date "2021-03-25" @default.
- W3139221490 modified "2023-10-12" @default.
- W3139221490 title "A genome-scale CRISPR Cas9 dropout screen identifies synthetically lethal targets in SRC-3 inhibited cancer cells" @default.
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