eIF2β, a subunit of translation-initiation factor EIF2, is a potential therapeutic target for non-small cell lung cancer.
eIF2β, a subunit of translation-initiation factor EIF2, is a potential therapeutic target for non-small cell lung cancer.
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DOI：
10.1111/cas.13602
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发表时间：
2018-06
期刊：
影响因子：
5.7
通讯作者：
Hasegawa Y
中科院分区：
文献类型：
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作者：
Tanaka I;Sato M;Kato T;Goto D;Kakumu T;Miyazawa A;Yogo N;Hase T;Morise M;Sekido Y;Girard L;Minna JD;Byers LA;Heymach JV;Coombes KR;Kondo M;Hasegawa Y
为了确定非小细胞肺癌（NSCLC）的新治疗靶点，我们进行了以下3个阶段的综合研究：（i）在2个独立的NSCLC细胞系中通过shRNA功能筛选鉴定潜在的靶基因;（ii）使用公共数据库验证鉴定的基因的临床相关性;（iii）在非小细胞肺癌（NSCLC）细胞系中通过shRNA功能筛选鉴定潜在的靶基因。和（iii）研究体外靶向鉴定的基因的治疗潜力。在NCI-H358细胞中进行了半基因组范围的shRNA筛选，并与我们之前在NCI-H460细胞中筛选的数据进行了整合。在shRNA筛选中鉴定的基因中，有24个基因存在于NCI-H358和NCI-H460细胞中，被认为是潜在的靶标。在这些基因中，我们重点关注eIF 2 β，它是异源三聚体G蛋白EIF 2的亚基，并作为转录起始因子发挥作用。与正常支气管上皮细胞相比，eIF 2 β蛋白在肺癌细胞系中高度表达，基因拷贝数分析显示，eIF 2 β在NSCLC细胞系亚群中扩增。使用癌症基因组图谱（TCGA）数据集进行的基因表达分析显示，与相应的正常肺组织相比，eIF 2 β在肺癌组织中的表达显著上调。此外，eIF 2 β高表达与肺腺癌患者的生存率低相关，如使用公开在线工具的其他队列所示。RNAi介导的eIF 2 β耗竭抑制肺癌细胞的生长，与p53突变状态无关，部分通过G1细胞周期停滞。我们的数据表明eIF 2 β是肺癌的治疗靶点。
To identify novel therapeutic targets for non‐small cell lung cancer (NSCLC), we conducted an integrative study in the following 3 stages: (i) identification of potential target gene(s) through shRNA functional screens in 2 independent NSCLC cell lines; (ii) validation of the clinical relevance of identified gene(s) using public databases; and (iii) investigation of therapeutic potential of targeting the identified gene(s) in vitro. A semi‐genome‐wide shRNA screen was performed in NCI‐H358 cells, and was integrated with data from our previous screen in NCI‐H460 cells. Among genes identified in shRNA screens, 24 were present in both NCI‐H358 and NCI‐H460 cells and were considered potential targets. Among the genes, we focused on eIF2β, which is a subunit of heterotrimeric G protein EIF2 and functions as a transcription initiation factor. The eIF2β protein is highly expressed in lung cancer cell lines compared with normal bronchial epithelial cells, and gene copy number analyses revealed that eIF2β is amplified in a subset of NSCLC cell lines. Gene expression analysis using The Cancer Genome Atlas (TCGA) dataset revealed that eIF2β expression is significantly upregulated in lung cancer tissues compared with corresponding normal lung tissues. Furthermore, high eIF2β expression was correlated with poor survival in patients with lung adenocarcinoma, as shown in other cohorts using publicly available online tools. RNAi‐mediated depletion of eIF2β suppresses growth of lung cancer cells independently of p53 mutation status, in part through G1 cell cycle arrest. Our data suggest that eIF2β is a therapeutic target for lung cancer.
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影响因子：
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作者：
Yuen HF;Chan KK;Platt-Higgins A;Dakir el-H;Matchett KB;Haggag YA;Jithesh PV;Habib T;Faheem A;Dean FA;Morgan R;Rudland PS;El-Tanani M
通讯作者：
El-Tanani M
DOI：
10.1097/jto.0000000000000560
发表时间：
2015-07
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Robles AI;Arai E;Mathé EA;Okayama H;Schetter AJ;Brown D;Petersen D;Bowman ED;Noro R;Welsh JA;Edelman DC;Stevenson HS;Wang Y;Tsuchiya N;Kohno T;Skaug V;Mollerup S;Haugen A;Meltzer PS;Yokota J;Kanai Y;Harris CC
通讯作者：
Harris CC
影响因子：
14.9
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.
DOI：
10.1158/1541-7786.mcr-12-0634-t
发表时间：
2013-06
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Sato M;Larsen JE;Lee W;Sun H;Shames DS;Dalvi MP;Ramirez RD;Tang H;DiMaio JM;Gao B;Xie Y;Wistuba II;Gazdar AF;Shay JW;Minna JD
通讯作者：
Minna JD
影响因子：
14.8
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.