| Item type |
文献 / Documents(1) |
| 公開日 |
2020-12-25 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1038/s41467-018-05626-2 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1038/s41467-018-05626-2 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Notch3-dependent β-catenin signaling mediates EGFR TKI drug persistence in EGFR mutant NSCLC |
|
言語 |
en |
| 著者 |
Arasada, Rajeswara Rao
Shilo, Konstantin
ヤマダ, タダアキ
Zhang, Jianying
ヤノ, セイジ
Ghanem, Rashelle
Wang, Walter
タケウチ, シンジ
フクダ, コウジ
カタカミ, ノブユキ
トミイ, ケイスケ
オオグシ, フミタカ
西岡, 安彦
Talabere, Tiffany
Misra, Shrilekha
Duan, Wenrui
Fadda, Paolo
Rahman, Mohammad A.
Nana-Sinkam, Patrick
Evans, Jason
Amann, Joseph
Tchekneva, Elena E.
Dikov, Mikhail M.
Carbone, David P.
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
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. |
|
言語 |
en |
| 書誌情報 |
en : Nature Communications
巻 9,
p. 3198,
発行日 2018-08-10
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20411723 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12645905 |
| 出版者 |
|
|
出版者 |
Springer Nature |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
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 |
| EID |
|
|
識別子 |
347643 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
ncomms_9_3198.pdf (5.56 MB)
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