| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2019-06-21 |
| タイトル |
|
|
タイトル |
NF-κB-induced NOX1 activation promotes gastric tumorigenesis through the expansion of SOX2-positive epithelial cells |
| 言語 |
|
|
言語 |
eng |
| 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 |
| ID登録 |
|
|
ID登録 |
10.24517/00053858 |
|
ID登録タイプ |
JaLC |
| 著者 |
Echizen, Kanae
Horiuchi, Keigo
Aoki, Yayoi
Yamada, Yoichi
Minamoto, Toshinari
Oshima, Hiroko
Oshima, Masanobu
|
| 著者別表示 |
源, 利成
大島, 浩子
大島, 正伸
|
| 提供者所属 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
金沢大学ナノ生命科学研究所 |
| 書誌情報 |
Oncogene
巻 38,
号 22,
p. 4250-4263,
発行日 2019-03-30
|
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0950-9232 |
| NCID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA10687380 |
| DOI |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1038/s41388-019-0702-0 |
| 出版者 |
|
|
出版者 |
Springer Nature |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
We previously showed that NADPH oxidase organizer 1 (Noxo1), a component of NADPH oxidase 1 (NOX1), is a TNF-α-induced tumor-promoting factor in gastric tumorigenesis. However, the mechanism of NOX1-induced reactive oxygen species (ROS) signaling for the gastric tumorigenesis has not been understood. Here, we showed that expression of NOX1 complex components, including Noxo1, but not other NOX family members was significantly upregulated in both mouse models for gastritis and gastric tumors, which was associated with increased ROS levels. We also found that NF-κB directly regulated NOXO1 expression in TNF-α-stimulated gastric cancer cells, suggesting that inflammation induces NOX1 complex activation through TNF-α/NF-κB pathway. Notably, in situ hybridization indicated that Noxo1 mRNA was detected in proliferating cells of gastritis and gastric tumors, and pharmacological inhibition of NOX activity significantly suppressed the proliferation of MKN45 gastric cancer cells and gastric hyperplasia of K19-C2mE mice. These results suggest that NOX1/ROS signaling has an important role in increased proliferation of stomach epithelial cells in the inflamed mucosa. Moreover, we found that expression of SOX2, a marker of gastric epithelial stem cells, was increased by NOX1/ROS signaling. Furthermore, disruption of Noxo1 in K19-C2mE mice significantly suppressed gastritis-associated metaplastic hyperplasia, a potent preneoplastic lesion, which was associated with decreased number of SOX2-positive cells. These results indicate that inflammation-induced Noxo1 expression is responsible for development of metaplastic hyperplasia in the stomach through an increase in SOX2-expressing undifferentiated epithelial cells. Therefore, inhibition of the NOX1/ROS signaling pathway is a possible strategy for prevention and therapy for gastric cancer development. © 2019, The Author(s). |
| 内容記述 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
Embargo Period 6 months |
| 権利 |
|
|
権利情報 |
Copyright © 2019, The Author(s). / Springer Nature |
| 著者版フラグ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連URI |
|
|
|
識別子タイプ |
URI |
|
|
関連識別子 |
https://www.nature.com/articles/s41388-019-0702-0 |
|
|
関連名称 |
https://www.nature.com/articles/s41388-019-0702-0 |
ME-PR-OSHIMA-M-4250.pdf (6.4 MB)
.png)
