| Item type |
文献 / Documents(1) |
| 公開日 |
2023-11-08 |
| 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/s41419-023-05768-2 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1038/s41419-023-05768-2 |
| 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 |
Inhibition of the mitochondria-shaping protein Opa1 restores sensitivity to Gefitinib in a lung adenocarcinomaresistant cell line |
|
言語 |
en |
| 著者 |
ノグチ, マサフミ
コウノ, ススム
Pellattiero, Anna
マチダ, ユキノ
柴田, 桂太朗
シンタニ, ノリヒト
コウノ, タカシ
ゴトウ, ノリコ
タカハシ, チアキ
ヒラオ, アツシ
Scorrano, Luca
カサハラ, アツコ
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Drug resistance limits the efficacy of chemotherapy and targeted cancer treatments, calling for the identification of druggable targets to overcome it. Here we show that the mitochondria-shaping protein Opa1 participates in resistance against the tyrosine kinase inhibitor gefitinib in a lung adenocarcinoma cell line. Respiratory profiling revealed that oxidative metabolism was increased in this gefitinib-resistant lung cancer cell line. Accordingly, resistant cells depended on mitochondrial ATP generation, and their mitochondria were elongated with narrower cristae. In the resistant cells, levels of Opa1 were increased and its genetic or pharmacological inhibition reverted the mitochondrial morphology changes and sensitized them to gefitinib-induced cytochrome c release and apoptosis. In vivo, the size of gefitinib-resistant lung orthotopic tumors was reduced when gefitinib was combined with the specific Opa1 inhibitor MYLS22. The combo gefitinib-MYLS22 treatment increased tumor apoptosis and reduced its proliferation. Thus, the mitochondrial protein Opa1 participates in gefitinib resistance and can be targeted to overcome it. |
|
言語 |
en |
| 書誌情報 |
en : Cell Death & Disease
巻 14,
p. 241,
発行日 2023-04-05
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20414889 |
| 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/. |
| EID |
|
|
識別子 |
400053 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
cdd_14_241.pdf (4.24 MB)
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