| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2018-04-05 |
| タイトル |
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|
タイトル |
Colorectal cancer cells require glycogen synthase kinase-3β for sustaining mitosis via translocated promoter region (TPR)- dynein interaction |
| 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 |
|
資源タイプ |
journal article |
| ID登録 |
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|
ID登録 |
10.24517/00050465 |
|
ID登録タイプ |
JaLC |
| 著者 |
Dewi, Firli R.P.
Domoto, Takahiro
Hazawa, Masaharu
Kobayashi, Akiko
Douwaki, Takayuki
Motohashi, Hozumi
Wong, Richard W.
|
| 著者別表示 |
堂本, 貴寛
羽澤, 勝治
小林, 亜紀子
源, 利成
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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 |
金沢大学がん進展制御研究所 |
| 書誌情報 |
Oncotarget
巻 9,
号 17,
p. 13337-13352,
発行日 2018
|
| 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 |
1949-2553 |
| DOI |
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関連タイプ |
isIdenticalTo |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
10.18632/oncotarget.24344 |
| 出版者 |
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出版者 |
Impact Journals LLC |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Glycogen synthase kinase (GSK) 3β, which mediates fundamental cellular signaling pathways, has emerged as a potential therapeutic target for many types of cancer including colorectal cancer (CRC). During mitosis, GSK3β localizes in mitotic spindles and centrosomes, however its function is largely unknown. We previously demonstrated that translocated promoter region (TPR, a nuclear pore component) and dynein (a molecular motor) cooperatively contribute to mitotic spindle formation. Such knowledge encouraged us to investigate putative functional interactions among GSK3β, TPR, and dynein in the mitotic machinery of CRC cells. Here, we show that inhibition of GSK3β attenuated proliferation, induced cell cycle arrest at G2/M phase, and increased apoptosis of CRC cells. Morphologically, GSK3β inhibition disrupted chromosome segregation, mitotic spindle assembly, and centrosome maturation during mitosis, ultimately resulting in mitotic cell death. These changes in CRC cells were associated with decreased expression of TPR and dynein, as well as disruption of their functional colocalization with GSK3β in mitotic spindles and centrosomes. Clinically, we showed that TPR expression was increased in CRC databases and primary tumors of CRC patients. Furthermore, TPR expression in SW480 cells xenografted into mice was reduced following treatment with GSK3β inhibitors. Together, these results indicate that GSK3β sustains steady mitotic processes for proliferation of CRC cells via interaction with TPR and dynein, thereby suggesting that the therapeutic effect of GSK3β inhibition depends on induction of mitotic catastrophe in CRC cells. © Dewi et al. |
| 内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
出版社版 |
| 権利 |
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|
権利情報 |
Copyright © Dewi et al. |
| 著者版フラグ |
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|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
CA-PR-MINAMOTO-T-13337.pdf (5.4 MB)
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