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TRPS1 Is a Lineage-Specific Transcriptional Dependency in Breast Cancer.
Cell Reports ( IF 7.5 ) Pub Date : 2018-10-30 , DOI: 10.1016/j.celrep.2018.10.023
Robert M Witwicki 1 , Muhammad B Ekram 1 , Xintao Qiu 2 , Michalina Janiszewska 1 , Shaokun Shu 1 , Mijung Kwon 3 , Anne Trinh 1 , Elizabeth Frias 4 , Nadire Ramadan 4 , Greg Hoffman 4 , Kristine Yu 4 , Yingtian Xie 2 , Gregory McAllister 4 , Rob McDonald 4 , Javad Golji 4 , Michael Schlabach 4 , Antoine deWeck 4 , Nicholas Keen 4 , Ho Man Chan 4 , David Ruddy 4 , Tomas Rejtar 4 , Sosathya Sovath 4 , Serena Silver 4 , William R Sellers 4 , Zainab Jagani 4 , Michael D Hogarty 5 , Charles Roberts 3 , Myles Brown 6 , Kimberly Stegmaier 3 , Henry Long 2 , Ramesh A Shivdasani 6 , David Pellman 3 , Kornelia Polyak 6
Cell Reports ( IF 7.5 ) Pub Date : 2018-10-30 , DOI: 10.1016/j.celrep.2018.10.023
Robert M Witwicki 1 , Muhammad B Ekram 1 , Xintao Qiu 2 , Michalina Janiszewska 1 , Shaokun Shu 1 , Mijung Kwon 3 , Anne Trinh 1 , Elizabeth Frias 4 , Nadire Ramadan 4 , Greg Hoffman 4 , Kristine Yu 4 , Yingtian Xie 2 , Gregory McAllister 4 , Rob McDonald 4 , Javad Golji 4 , Michael Schlabach 4 , Antoine deWeck 4 , Nicholas Keen 4 , Ho Man Chan 4 , David Ruddy 4 , Tomas Rejtar 4 , Sosathya Sovath 4 , Serena Silver 4 , William R Sellers 4 , Zainab Jagani 4 , Michael D Hogarty 5 , Charles Roberts 3 , Myles Brown 6 , Kimberly Stegmaier 3 , Henry Long 2 , Ramesh A Shivdasani 6 , David Pellman 3 , Kornelia Polyak 6
Affiliation
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Perturbed epigenomic programs play key roles in tumorigenesis, and chromatin modulators are candidate therapeutic targets in various human cancer types. To define singular and shared dependencies on DNA and histone modifiers and transcription factors in poorly differentiated adult and pediatric cancers, we conducted a targeted shRNA screen across 59 cell lines of 6 cancer types. Here, we describe the TRPS1 transcription factor as a strong breast cancer-specific hit, owing largely to lineage-restricted expression. Knockdown of TRPS1 resulted in perturbed mitosis, apoptosis, and reduced tumor growth. Integrated analysis of TRPS1 transcriptional targets, chromatin binding, and protein interactions revealed that TRPS1 is associated with the NuRD repressor complex. These findings uncover a transcriptional network that is essential for breast cancer cell survival and propagation.
中文翻译：
TRPS1是乳腺癌中特定于谱系的转录依赖性。
扰动的表观基因组程序在肿瘤发生中起关键作用，并且染色质调节剂是各种人类癌症类型的候选治疗靶标。为了定义低分化成年和小儿癌症中对DNA和组蛋白修饰物以及转录因子的单一和共有依赖性，我们针对6种癌症类型的59种细胞系进行了靶向shRNA筛选。在这里，我们将TRPS1转录因子描述为一种强烈的乳腺癌特异性命中因子，这在很大程度上归因于谱系限制的表达。击倒TRPS1会导致有丝分裂，细胞凋亡和肿瘤生长减少。对TRPS1转录靶标，染色质结合和蛋白质相互作用的综合分析表明，TRPS1与NuRD阻遏物复合物相关。
更新日期：2018-11-02
中文翻译：
TRPS1是乳腺癌中特定于谱系的转录依赖性。
扰动的表观基因组程序在肿瘤发生中起关键作用，并且染色质调节剂是各种人类癌症类型的候选治疗靶标。为了定义低分化成年和小儿癌症中对DNA和组蛋白修饰物以及转录因子的单一和共有依赖性，我们针对6种癌症类型的59种细胞系进行了靶向shRNA筛选。在这里，我们将TRPS1转录因子描述为一种强烈的乳腺癌特异性命中因子，这在很大程度上归因于谱系限制的表达。击倒TRPS1会导致有丝分裂，细胞凋亡和肿瘤生长减少。对TRPS1转录靶标，染色质结合和蛋白质相互作用的综合分析表明，TRPS1与NuRD阻遏物复合物相关。
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