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J-GLOBAL ID：202002217247633577   整理番号：20A2201673

SFPQ枯渇は,大腸癌細胞においてBRAF→γV600Eと合成的に致死性である【JST・京大機械翻訳】

SFPQ Depletion Is Synthetically Lethal with BRAF^V600E in Colorectal Cancer Cells

著者 (38件)： Klotz-Noack Kathleen (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Klotz-Noack Kathleen (German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany) ,  Klinger Bertram (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Klinger Bertram (IRI Life Sciences & Institute of Theoretical Biology, Humboldt-Universitaet zu Berlin, 10115 Berlin, Germany) ,  Rivera Maria (EPO Experimentelle Pharmakologie und Onkologie Berlin-Buch GmbH, Robert-Rossle-Str. 10, 13125 Berlin, Germany) ,  Bublitz Natalie (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Bublitz Natalie (German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany) ,  Uhlitz Florian (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Uhlitz Florian (IRI Life Sciences & Institute of Theoretical Biology, Humboldt-Universitaet zu Berlin, 10115 Berlin, Germany) ,  Riemer Pamela (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Luethen Mareen (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Luethen Mareen (German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany) ,  Sell Thomas (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Sell Thomas (IRI Life Sciences & Institute of Theoretical Biology, Humboldt-Universitaet zu Berlin, 10115 Berlin, Germany) ,  Kasack Katharina (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Kasack Katharina (German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany) ,  Gastl Bastian (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Ispasanie Sylvia S.S. (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Simon Tincy (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Janssen Nicole (Dr. Margarete Fischer-Bosch - Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376 Stuttgart, Germany) ,  Janssen Nicole (University of Tuebingen, 72074 Tuebingen, Germany) ,  Schwab Matthias (Dr. Margarete Fischer-Bosch - Institute of Clinical Pharmacology, Auerbachstrasse 112, 70376 Stuttgart, Germany) ,  Schwab Matthias (Departments of Clinical Pharmacology, Pharmacy and Biochemistry, University of Tuebingen, Auf der Morgenstelle 8, 72074 Tuebingen, Germany) ,  Schwab Matthias (German Cancer Consortium (DKTK), Partner Site Tuebingen and German Cancer Research Center (DKFZ), Heidelberg, Germany) ,  Zuber Johannes (Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), 1030 Vienna, Austria) ,  Zuber Johannes (Medical University of Vienna, VBC, 1030 Vienna, Austria) ,  Horst David (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Horst David (German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany) ,  Bluethgen Nils (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Bluethgen Nils (IRI Life Sciences & Institute of Theoretical Biology, Humboldt-Universitaet zu Berlin, 10115 Berlin, Germany) ,  Bluethgen Nils (German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany) ,  Schaefer Reinhold (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Schaefer Reinhold (German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany) ,  Schaefer Reinhold (Charite Comprehensive Cancer Center, Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health, Chariteplatz 1, 10117 Berlin, Germany) ,  Morkel Markus (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Morkel Markus (German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany) ,  Sers Christine (Charite - Universitaetsmedizin Berlin, corporate member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, and Berlin Institute of Health. Laboratory of Molecular Tumor Pathology and Systems Biology, Institute of Pathology, 10117 Berlin, Germany) ,  Sers Christine (German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany)
資料名： Cell Reports  (Cell Reports)
巻： 32  号： 12  ページ： Null  発行年： 2020年 
JST資料番号： W3124A  ISSN： 2211-1247  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： BRAFV600Eキナーゼのような癌蛋白質は悪性特性を有する癌細胞を与えるが,それらはユニークな脆弱性も生成する。BRAFV600E駆動細胞質シグナル伝達ネットワークの標的化は,標的経路の再活性化で規則的に再発するので,無効であることが証明されている。機能喪失shRNAスクリーニングにおいてBRAFV600Eで合成的に致死する核蛋白質SFPQを同定した。SFPQ枯渇は増殖を減少させ,BRAFV600E駆動結腸直腸とメラノーマ細胞でS期停止とアポトーシスを特異的に誘導する。機構的に,BRAF変異癌細胞におけるSFPQ損失は,Chk1依存性複製チェックポイントを誘発し,複製工場の数の減少と活性の低下をもたらし,複製と転写の間の衝突を増加させる。BRAFV600E変異癌細胞とオルガノイドは,Chk1阻害剤と化学的誘導複製ストレスの組み合わせに感受性であり,BRAFV600Eにより誘導される核脆弱性を利用する将来の治療方法を示すことを見出した。Copyright 2020 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： 核タンパク質 ,  細胞質 ,  *腫瘍細胞 ,  スクリーニング ,  ターゲティング ,  アポトーシス ,  癌タンパク質
準シソーラス用語： オルガノイド ,  *プロトオンコジーン蛋白質B-raf ,  S期 ,  チェックポイントキナーゼ1 ,  *大腸癌細胞 ,  再活性化 ,  キナーゼ , 【Automatic Indexing@JST】

著者キーワード (9件)： MAPKシグナリング ,  Chk1 ,  複製ストレス ,  Rループ ,  細胞死 ,  合成致死率 ,  DNA損傷 ,  異種移植 ,  オルガノイド

分類 (4件)： 内分泌系の腫よう  (GL04000P) ,  抗腫よう薬の基礎研究  (GW16010A) ,  腫ようの化学・生化学・病理学  (GE02030N) ,  遺伝子発現  (EC02040Q)

タイトルに関連する用語 (3件)： 枯渇 ,  大腸癌細胞 ,  BRAF