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ID 114785
著者
Arasada, Rajeswara Rao The Ohio State University
Shilo, Konstantin The Ohio State University
Yamada, Tadaaki Kanazawa University
Zhang, Jianying The Ohio State University
Yano, Seiji Kanazawa University
Ghanem, Rashelle The Ohio State University
Wang, Walter The Ohio State University
Takeuchi, Shinji Kanazawa University
Fukuda, Koji Kanazawa University
Katakami, Nobuyuki Institute of Biomedical Research and Innovation
Tomii, Keisuke Kobe City Medical Center General Hospital
Ogushi, Fumitaka National Hospital Organization National Kochi Hospital
Talabere, Tiffany The Ohio State University
Misra, Shrilekha The Ohio State University
Duan, Wenrui The Ohio State University
Fadda, Paolo The Ohio State University
Rahman, Mohammad A. The Ohio State University
Nana-Sinkam, Patrick The Ohio State University
Evans, Jason The Ohio State University
Amann, Joseph The Ohio State University
Tchekneva, Elena E. The Ohio State University
Dikov, Mikhail M. The Ohio State University
Carbone, David P. The Ohio State University
資料タイプ
学術雑誌論文
抄録
EGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung cancer, but resistance universally develops. The involvement of β-catenin in EGFR TKI resistance has been previously reported, however, the precise mechanism by which β-catenin activation contributes to EGFR TKI resistance is not clear. Here, we show that EGFR inhibition results in the activation of β-catenin signaling in a Notch3-dependent manner, which facilitates the survival of a subset of cells that we call “adaptive persisters”. We previously reported that EGFR-TKI treatment rapidly activates Notch3, and here we describe the physical association of Notch3 with β-catenin, leading to increased stability and activation of β-catenin. We demonstrate that the combination of EGFR-TKI and a β-catenin inhibitor inhibits the development of these adaptive persisters, decreases tumor burden, improves recurrence free survival, and overall survival in xenograft models. These results supports combined EGFR-TKI and β-catenin inhibition in patients with EGFR mutant lung cancer.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
9
開始ページ
3198
発行日
2018-08-10
権利情報
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2018
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言語
eng
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出版社版
部局
医学系