| Item type |
文献 / Documents(1) |
| 公開日 |
2025-04-11 |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 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 |
|
|
|
関連識別子 |
https://doi.org/10.1080/23723556.2024.2377404 |
|
|
関連名称 |
10.1080/23723556.2024.2377404 |
| 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 |
Amino acid deprivation in cancer cells with compensatory autophagy induction increases sensitivity to autophagy inhibitors |
| 著者 |
Fukui, Takahito
Yabumoto, Manami
Nishida, Misuzu
Hirokawa, Shiori
Sato, Riho
Kurisu, Taichi
Nakai, Miyu
Hassan, Md. Abul
岸本, 幸治
|
| 抄録 |
|
|
内容記述 |
Inhibition of autophagy is an important strategy in cancer therapy. However, prolonged inhibition of certain autophagies in established cancer cells may increase therapeutic resistance, though the underlying mechanisms of its induction and enhancement remain unclear. This study sought to elucidate the mechanisms of therapeutic resistance through repeated autophagy inhibition and amino acid deprivation (AD) in an in vitro model of in vivo chronic nutrient deprivation associated with cancer cell treatment. In the human cervical cancer cell line HeLa and human breast cancer cell line MCF-7, initial extracellular AD induced the immediate expression of endosomal microautophagy (eMI). However, repeated inhibition of eMI with U18666A and extracellular AD induced macroautophagy (MA) to compensate for reduced eMI, simultaneously decreasing cytotoxicity. Here, hyperphosphorylated JNK was transformed into a hypophosphorylated state, suggesting conversion of the cell death signal to a survival signal. In a nutrient medium, cell death could not be induced by MA inhibition. However, since LAT1 inhibitors induce intracellular AD, combining them with MA and eMI inhibitors successfully promoted cell death in resistant cells. Our study identified a novel therapeuic approach for promoting cell death and addressing therapeutic resistance in cancers under autophagy-inhibitor treatment. |
| キーワード |
|
|
主題 |
Amino acid deprivation |
| キーワード |
|
|
主題 |
amino acid transporter |
| キーワード |
|
|
主題 |
autophagy |
| キーワード |
|
|
主題 |
cancer |
| キーワード |
|
|
主題 |
chemoresistance |
| 書誌情報 |
en : Molecular & Cellular Oncology
巻 11,
号 1,
p. 2377404,
発行日 2024-07-14
|
| 収録物ID |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
23723556 |
| 出版者 |
|
|
出版者 |
Taylor & Francis |
| 権利情報 |
|
|
権利情報 |
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. |
| EID |
|
|
識別子 |
417133 |
| 言語 |
|
|
言語 |
eng |
mco_11_1_2377404.pdf (4.6 MB)
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