| Item type |
文献 / Documents(1) |
| 公開日 |
2019-03-05 |
| 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/10.18632/oncotarget.11830 |
|
|
言語 |
ja |
|
|
関連名称 |
10.18632/oncotarget.11830 |
| 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 |
The iron chelator deferasirox induces apoptosis by targeting oncogenic Pyk2/β-catenin signaling in human multiple myeloma |
|
言語 |
en |
| 著者 |
カミハラ, ユウスケ
タカダ, コウイチ
サトウ, ツトム
カワノ, ユタカ
ムラセ, カズユキ
アリハラ, ヨウヘイ
キクチ, ショウヘイ
ハヤサカ, ナオタカ
ウサミ, マコト
イヤマ, サトシ
ミヤニシ, コウジ
佐藤, 康史
コブネ, マサヨシ
カトウ, ジュンジ
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Deregulated iron metabolism underlies the pathogenesis of many human cancers. Recently, low expression of ferroportin, which is the only identified non-heme iron exporter, has been associated with significantly reduced overall survival in multiple myeloma (MM); however, the altered iron metabolism in MM biology remains unclear. In this study we demonstrated, by live cell imaging, that MM cells have increased intracellular iron levels as compared with normal cells. In experiments to test the effect of iron chelation on the growth of MM cells, we found that deferasirox (DFX), an oral iron chelator used to treat iron overload in clinical practice, inhibits MM cell growth both in vivo and in vitro. Mechanistically, DFX was found to induce apoptosis of MM cells via the inhibition of proline-rich tyrosine kinase 2 (Pyk2), which is known to promote tumor growth in MM. Inhibition of Pyk2 is caused by the suppression of reactive oxygen species, and leads to downregulation of the Wnt/β-catenin signaling pathway. Taken together, our findings indicate that high levels of intracellular iron, which might be due to low ferroportin expression, play a role in MM pathophysiology. Therefore, DFX may provide a therapeutic option for MM that is driven by deregulated iron homeostasis and/or Pyk2/Wnt signaling. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
deferasirox |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Pyk2 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
β-catenin |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
apoptosis |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
multiple myeloma |
| 書誌情報 |
en : Oncotarget
巻 7,
号 39,
p. 64330-64341,
発行日 2016-09-02
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
19492553 |
| 出版者 |
|
|
出版者 |
Impact Journals, LLC |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
|
|
識別子 |
332773 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
onc_7_39_64330.pdf (5.79 MB)
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