| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2019-04-25 |
| タイトル |
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タイトル |
Stat3 is indispensable for damage-induced crypt regeneration but not for Wnt-driven intestinal tumorigenesis. |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| ID登録 |
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|
ID登録 |
10.24517/00053860 |
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ID登録タイプ |
JaLC |
| 著者 |
Oshima, Hiroko
Kok, Sau-Yee
Nakayama, Mizuho
Murakami, Kazuhiro
Voon, Dominic Chih-Cheng
Kimura, Takashi
Oshima, Masanobu
|
| 著者別表示 |
大島, 浩子
中山, 瑞穂
村上, 和弘
大島, 正伸
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| 提供者所属 |
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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 |
FASEB journal
巻 33,
号 2,
p. 1873-1886,
発行日 2019-02-01
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| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0892-6638 |
| NCID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA1066874X |
| DOI |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
10.1096/fj.201801176R |
| 出版者 |
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出版者 |
Federation of American Society of Experimental Biology (FASEB) |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Signal transducer and activator of transcription 3 (Stat3) has been shown to play a role in intestinal regeneration and colitis-associated colon carcinogenesis. However, the role of Stat3 in the Wnt-driven sporadic intestinal tumorigenesis remains poorly understood. We examined the roles of Stat3 in intestinal regeneration and tumorigenesis by organoid culture experiments using Stat3∆IEC mouse-derived intestinal epithelial cells in which Stat3 was disrupted. The regeneration of intestinal mucosa and organoid formation were significantly suppressed by Stat3 disruption, which was compensated by Wnt activation. Furthermore, once organoids were recovered, Stat3 was no longer required for organoid growth. These results indicate that Stat3 and Wnt signaling cooperatively protect epithelial cells at the early phase of intestinal regeneration. In contrast, intestinal tumorigenesis was not suppressed by Stat3 disruption in adenomatous polyposis coli ( Apc) Δ716 and Apc∆716 Tgfbr2∆IEC mice, thus indicating that Stat3 is not required for Wnt activation-driven intestinal tumorigenesis. Mechanistically, Itga5 and Itga6 were down-regulated by Stat3 disruption, and focal adhesion kinase (FAK) activation was also suppressed. Notably, FAK inhibitor suppressed the organoid formation of wild-type epithelial cells. These results indicate that Stat3 is indispensable for the survival of epithelial cells through the activation of integrin signaling and the downstream FAK pathway; however, it is not required for the Wnt signaling-activated normal or tumor epithelial cells.-Oshima, H., Kok, S.-Y., Nakayama, M., Murakami, K., Voon, D. C.-C., Kimura, T., Oshima, M. Stat3 is indispensable for damage-induced crypt regeneration but not for Wnt-driven intestinal tumorigenesis. |
| 権利 |
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権利情報 |
Copyright © Federation of American Society of Experimental Biology (FASEB) |
| 著者版フラグ |
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出版タイプ |
AM |
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出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連URI |
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識別子タイプ |
URI |
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関連識別子 |
https://www.fasebj.org/doi/10.1096/fj.201801176R |
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関連名称 |
https://www.fasebj.org/doi/10.1096/fj.201801176R |
ME-PR-OSHIMA-M-1873.pdf (1.8 MB)
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