| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-02-18 |
| タイトル |
|
|
タイトル |
Hypoxia-inducible hexokinase-2 enhances anti-apoptotic function via activating autophagy in multiple myeloma |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
autophagy |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
HK2 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
hypoxia |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
microenvironment |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
multiple myeloma |
| 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 |
| 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 |
| 作成者 |
Ikeda, Sho
Abe, Fumito
Matsuda, Yuka
Kitadate, Akihiro
Takahashi, Naoto
Tagawa, Hiroyuki
|
| 内容記述 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Multiple myeloma (MM) is an incurable hematopoietic neoplasm derived from plasma cells, and existing in the bone marrow. Recent developments in the field of myeloma onco-biology have enabled the use of proteasome inhibitors (PIs) as key drugs for MM. PIs can increase cell sensitivity to endoplasmic reticulum stress, leading to apoptosis of myeloma cells. PI cannot kill all myeloma cells, however; one reason of this might be activation of autophagy via hypoxic stress in the bone marrow microenvironment. Hypoxia-inducible gene(s) that regulate autophagy may be novel therapeutic target(s) for PI-resistant myeloma cells. Here, a hypoxia-inducible glycolytic enzyme hexokinase-2 (HK2) was demonstrated to contribute by autophagy activation to the acquisition of an anti-apoptotic phenotype in myeloma cells. We found that hypoxic stress led to autophagy activation accompanied by HK2 upregulation in myeloma cells. Under hypoxic conditions, HK2 knockdown inhibited glycolysis and impaired autophagy, inducing apoptosis. The cooperative effects of a PI (bortezomib) against immunodeficient mice inoculated with HK2-knocked down myeloma cells were examined and significant tumor reduction was observed. An HK2 inhibitor, 3-bromopyruvate (3-BrPA), also induced apoptosis under hypoxic rather than normoxic conditions. Further examination of the cooperative effects between 3-BrPA and bortezomib on myeloma cells revealed a significant increase in apoptotic myeloma cells. These results strongly suggested that HK2 regulates the activation of autophagy in hypoxic myeloma cells. Cooperative treatment using PI against a dominant fraction, and HK2 inhibitor against a minor fraction, adapted to the bone marrow microenvironment, may lead to deeper remission for refractory MM. |
|
言語 |
en |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 書誌情報 |
en : Cancer Science
巻 111,
号 11,
p. 4088-4101,
発行日 2020
|
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
13479032 |
| 出版者 |
|
|
出版者 |
John Wiley and Sons Inc |
| 関連情報 |
|
|
関連タイプ |
isIdenticalTo |
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|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1111/cas.14614 |
| 権利情報 |
|
|
権利情報 |
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. |
iA_2022_29.pdf (2.9 MB)
