| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-02-19 |
| タイトル |
|
|
タイトル |
Expression of asporin reprograms cancer cells to acquire resistance to oxidative stress |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
asporin |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
gastric cancer |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
HIF1 alpha |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
oxidative stress |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
ROS |
| 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 |
Sasaki, Yuto
Takagane, Kurara
Konno, Takumi
Itoh, Go
Kuriyama, Sei
Yanagihara, Kazuyoshi
Yashiro, Masakazu
Yamada, Satoru
Murakami, Shinya
Tanaka, Masamitsu
|
| 内容記述 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Asporin (ASPN), a small leucine-rich proteoglycan expressed predominantly by cancer associated fibroblasts (CAFs), plays a pivotal role in tumor progression. ASPN is also expressed by some cancer cells, but its biological significance is unclear. Here, we investigated the effects of ASPN expression in gastric cancer cells. Overexpression of ASPN in 2 gastric cancer cell lines, HSC-43 and 44As3, led to increased migration and invasion capacity, accompanied by induction of CD44 expression and activation of Rac1 and MMP9. ASPN expression increased resistance of HSC-43 cells to oxidative stress by reducing the amount of mitochondrial reactive oxygen species. ASPN induced expression of the transcription factor HIF1 alpha and upregulated lactate dehydrogenase A (LDHA) and PDH-E1 alpha, suggesting that ASPN reprograms HSC-43 cells to undergo anaerobic glycolysis and suppresses ROS generation in mitochondria, which has been observed in another cell line HSC-44PE. By contrast, 44As3 cells expressed high levels of HIF1 alpha in response to oxidant stress and escaped apoptosis regardless of ASPN expression. Examination of xenografts in the gastric wall of ASPN(-/-) mice revealed that growth of HSC-43 tumors with increased micro blood vessel density was significantly accelerated by ASPN; however, ASPN increased the invasion depth of both HSC-43 and 44As3 tumors. These results suggest that ASPN has 2 distinct effects on cancer cells: HIF1 alpha-mediated resistance to oxidative stress via reprogramming of glucose metabolism, and activation of CD44-Rac1 and MMP9 to promote cell migration and invasion. Therefore, ASPN may be a new therapeutic target in tumor fibroblasts and cancer cells in some gastric carcinomas. |
|
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 112,
号 3,
p. 1251-1261,
発行日 2021
|
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1347-9032 |
| 出版者 |
|
|
出版者 |
John Wiley and Sons Inc |
| 関連情報 |
|
|
関連タイプ |
isIdenticalTo |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1111/cas.14794 |
| 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.© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. |
iA_2022_38.pdf (2.1 MB)
