A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells

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A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells

机译：全基因组的siRNA屏幕将蛋白酶体成瘾确定为基底样三阴性乳腺癌细胞的脆弱性。

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Basal-like triple-negative breast cancers (TNBCs) have poor prognosis. To identify basal-like TNBC dependencies, a genome-wide siRNA lethality screen compared two human breast epithelial cell lines transformed with the same genes: basal-like BPLER and myoepithelial HMLER. Expression of the screen's 154 BPLER dependency genes correlated with poor prognosis in breast, but not lung or colon, cancer. Proteasome genes were overrepresented hits. Basal-like TNBC lines were selectively sensitive to proteasome inhibitor drugs relative to normal epithelial, luminal, and mesenchymal TNBC lines. Proteasome inhibition reduced growth of established basal-like TNBC tumors in mice and blocked tumor-initiating cell function and macrometastasis. Proteasome addiction in basal-like TNBCs was mediated by NOXA and linked to MCL-1 dependence.

机译：基底样三阴性乳腺癌（TNBC）的预后较差。为了鉴定基底样TNBC依赖性，全基因组siRNA致死率筛选比较了用相同基因转化的两种人乳腺上皮细胞系：基底样BPLER和肌上皮HMLER。筛选的154个BPLER依赖性基因的表达与乳腺癌（而非肺癌或结肠癌）的不良预后相关。蛋白酶体基因被高估。相对于正常上皮，管腔和间质TNBC系，基底样TNBC系对蛋白酶体抑制剂药物选择性敏感。蛋白酶体抑制作用降低了小鼠已建立的基底样TNBC肿瘤的生长，并阻断了肿瘤引发的细胞功能和宏观转移。基底样TNBCs中的蛋白酶体成瘾是由NOXA介导的，并且与MCL-1依赖性有关。

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《Cancer Cell》 |2013年第2期|共15页
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1. A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells [J] . Cancer Cell . 2013,第2期

机译：全基因组的siRNA屏幕将蛋白酶体成瘾确定为基底样三阴性乳腺癌细胞的脆弱性。
2. Truncated HDAC9 identified by integrated genome-wide screen as the key modulator for paclitaxel resistance in triple-negative breast cancer [J] . Bi Lian, Yu-Chen Pei, Yi-Zhou Jiang, Theranostics . 2020,第24期

机译：截断的HDAC9通过综合基因组屏幕鉴定为三阴性乳腺癌中紫杉醇抗性的关键调节剂
3. Seed-effect modeling improves the consistency of genome-wide loss-of-function screens and identifies synthetic lethal vulnerabilities in cancer cells [J] . Alok Jaiswal, Gopal Peddinti, Yevhen Akimov, Genome Medicine . 2017,第1期

机译：种子效应建模可改善全基因组功能丧失筛选的一致性，并识别癌细胞中的合成致死性漏洞
4. Identifying Effective siRNAs for Polymer-Mediated Combinatorial Delivery to Drug Sensitive and Resistant Breast Cancer Cells [C] . H.M. Aliabadi, P. Mahdipoor, H. Uludag Society for Biomaterials annual meeting and exposition . 2014

机译：鉴定有效的siRNA，用于聚合物介导的组合递送至药物敏感性和耐药性乳腺癌细胞
5. 14-3-3sigma Expression Identifies Basal-Like Breast Cancer and Regulates Tumor Invasion by Defining Subcellular Regions of Actin Polymerization. [D] . Boudreau, Aaron Thomas. 2010

机译：14-3-3sigma表达可识别基底样乳腺癌，并通过定义肌动蛋白聚合的亚细胞区域来调节肿瘤侵袭。
6. A genome-wide siRNA screen identifies proteasome addiction as a vulnerability of basal-like triple-negative breast cancer cells [O] . Fabio Petrocca, Gabriel Altschuler, Shen Mynn Tan, -1

机译：全基因组的siRNA筛查将蛋白酶体成瘾识别为基底样三阴性乳腺癌细胞的脆弱性
7. A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells [O] . Petrocca Fabio, Altschuler Gabriel, Tan Shen Mynn, 2013

机译：全基因组的siRNA屏幕将蛋白酶体成瘾确定为基底样三阴性乳腺癌细胞的脆弱性。

A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells

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