| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2017-10-05 |
| タイトル |
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タイトル |
Aberrant Glycogen Synthase Kinase 3β Is Involved in Pancreatic Cancer Cell Invasion and Resistance to Therapy |
| 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 |
10.24517/00027437 |
|
ID登録タイプ |
JaLC |
| 著者 |
Kitano, Ayako
Shimasaki, Takeo
Chikano, Yuri
Nakada, Mitsutoshi
Hirose, Mayumi
Higashi, Tomomi
Ishigaki, Yasuhito
Endo, Yoshio
Takino, Takahisa
Sato, Hiroshi
Sai, Yoshimichi
Miyamoto, Ken-ichi
Motoo, Yoshiharu
Kawakami, Kazuyuki
Minamoto, Toshinari
|
| 著者別表示 |
中田, 光俊
廣瀬, まゆみ
東, 朋美
石垣, 靖人
遠藤, 良夫
滝野, 隆久
佐藤, 博
崔, 吉道
宮本, 謙一
元雄, 良治
川上, 和之
源, 利成
|
| 書誌情報 |
PLoS ONE
巻 8,
号 2,
p. e55289,
発行日 2013-02-08
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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 |
1932-6203 |
| 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 |
10.1371/journal.pone.0055289 |
| 出版者 |
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出版者 |
PLoS ONE |
| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Background and Purpose: The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer. Methods: Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined. Results: Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts. Conclusion: The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer. © 2013 Kitano 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 |
| 関連URI |
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識別子タイプ |
URI |
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関連識別子 |
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0055289 |
CA-PR-MINAMOTO-T-55289-2013.pdf (2.4 MB)
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