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J-GLOBAL ID：202202258410269444   整理番号：22A0968234

SOX17とPAX8は卵巣癌において作用可能な系列生存転写複合体を構成する【JST・京大機械翻訳】

SOX17 and PAX8 constitute an actionable lineage-survival transcriptional complex in ovarian cancer

著者 (32件)： Lin Lifeng (Ovarian Cancer Program, Department of Gynecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai, China) ,  Shi Kaixuan (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Shi Kaixuan (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Zhou Shaoqing (Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China) ,  Zhou Shaoqing (University of Chinese Academy of Sciences, Beijing, China) ,  Cai Mei-Chun (State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Zhang Caiyan (State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Sun Yunheng (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Sun Yunheng (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Zang Jingyu (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Zang Jingyu (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Cheng Lin (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Cheng Lin (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Ye Kaiyan (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Ye Kaiyan (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Ma Pengfei (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Ma Pengfei (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Shen Peiye (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Shen Peiye (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Zhang Meiying (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Zhang Meiying (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Cheng Yan (Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China) ,  Qi Chunting (Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China) ,  Li Ying (Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China) ,  Yin Xia (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Yin Xia (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Zheng Yiyan (Ovarian Cancer Program, Department of Gynecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai, China) ,  Tan Li (Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China) ,  Tan Li (University of Chinese Academy of Sciences, Beijing, China) ,  Zhuang Guanglei (State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Zhuang Guanglei (Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) ,  Zang Rongyu (Ovarian Cancer Program, Department of Gynecologic Oncology, Zhongshan Hospital, Fudan University, Shanghai, China)
資料名： Oncogene  (Oncogene)
巻： 41  号： 12  ページ： 1767-1779  発行年： 2022年 
JST資料番号： T0406A  ISSN： 0950-9232  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： ドイツ (DEU)  言語： 英語 (EN)

抄録/ポイント： PAX8によりプロトタイプ化されたミュラー組織特異的癌遺伝子は,卵巣腫瘍形成を基盤とし,ユニークな分子脆弱性を示す。このような系統依存性因子および関連する治療含意を更に描写することは,卵巣癌生物学および治療への貴重な洞察を提供する。本研究では,上皮卵巣癌においてPAX8と共発現パターンを共有する新しい系統生存マスター転写因子としてSOX17を同定した。SOX17またはPAX8の遺伝子破壊は,腫瘍細胞生存性を類似に阻害し,系統関連転写物のスペクトルをダウンレギュレートした。機構的に,SOX17は培養細胞株および臨床腫瘍標本においてPAX8と物理的に相互作用することを示した。2核蛋白質は重複ゲノム領域に結合し,細胞周期および組織形態形成に関与するものを含む下流遺伝子の共通セットを調節した。さらに,転写サイクリン依存性キナーゼ(CDK)の小分子阻害剤がSOX17とPAX8発現を効果的に減少させることを明らかにした。新規経口生物利用性CDK12/13共有結合アンタゴニストであるZSQ1722は異種移植モデルにおいて強力な抗腫瘍活性を発揮した。これらの知見は,卵巣癌における作用可能な系統-生存転写複合体に光を当て,この困難な治療悪性腫瘍を薬理学的に標的にする一連の候補化合物を生成することによって,薬物発見を容易にした。Copyright The Author(s), under exclusive licence to Springer Nature Limited 2022 Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： 相互作用 ,  抗腫瘍作用 ,  腫瘍 ,  上皮 ,  *転写【遺伝】 ,  *卵巣 ,  *複合体 ,  細胞周期 ,  形態形成 ,  異種移植 ,  癌遺伝子 ,  遺伝子発現 ,  *卵巣腫瘍 ,  転写因子
準シソーラス用語： 悪性腫瘍 ,  共発現 , 【Automatic Indexing@JST】

分類 (2件)： 腫ようの化学・生化学・病理学  (GE02030N) ,  女性生殖器と胎児の腫よう  (GS04000K)

タイトルに関連する用語 (7件)： Sox17 ,  Pax8 ,  卵巣癌 ,  系列 ,  生存 ,  転写 ,  複合体