Exploring biological basis of aberrant energy metabolic property of gastrointestinal cancer toward application to cancer treatment
Project/Area Number |
25860233
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pathological medical chemistry
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Research Institution | Kanazawa University |
Principal Investigator |
Domoto Takahiro 金沢大学, がん進展制御研究所, 助教 (80635540)
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Research Collaborator |
MINAMOTO TOSHINARI 金沢大学, がん進展制御研究所, 教授 (50239323)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | がん代謝 / 分子標的治療 / リン酸化 / GSK3beta / GSK3β |
Outline of Final Research Achievements |
We have identified aberrant GSK3beta as an attractive therapeutic target in various cancer types. Here we explored the mechanism for the tumor-promoting role of GSK3beta by focusing on the distinct energy metabolic property in cancer. We found that GSK3beta deregulated in cancer cells and their xenografts phosphorylates and inactivates pyruvate dehydrogenase (PDH)-E1alpha, the active subunit of PDH. This results in induction of the aerobic glycolysis that preferentially fuels cancer cells, leading to progression of cancer. Inhibition of GSK3beta shifted the energy source of cancer cells from glycolysis to oxidative phosphorylation in mitochondria, rendering them susceptible to apoptotic insults. No such metabolic changes were observed in non-neoplastic cells or rodent’s liver. Our results suggests that cancer therapeutic effect of GSK3beta inhibition depends on the exclusive metabolic shift in cancer cells, which reinforces the safety of targeting GSK3beta for cancer treatment.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1, and c-Jun N-terminal kinase-mediated pathway.2015
Author(s)
Yuri Chikano, Takahiro Domoto, Takuya Furuta, Hemragul Sabit, Ayako Kitano-Tamura, Ilya V. Pyko, Takahisa Takino,Yoshimichi Sai, Yutaka Hayashi, Hiroshi Sato, Ken-ichi Miyamoto, Mitsutoshi Nakada, Toshinari Minamoto
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Journal Title
Molecular Cancer Therapeutics
Volume: 14
Pages: 564-574
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] GSK3β阻害によるβ-カテニン活性化の骨肉腫治療効果2015
Author(s)
下﨑真吾, 山本憲男, 林 克洋, 木村浩明, 武内章彦, 三輪真嗣, 稲谷弘幸, 青木 裕, 樋口貴史, 阿部健作, 堂本貴寛, 大塚隆信, 源 利成, 土屋弘行
Organizer
第53回日本癌治療学会学術集会
Place of Presentation
京都市・国立京都国際会館
Year and Date
2015-10-29 – 2015-10-31
Related Report
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[Presentation] 大腸がん糖代謝特性におけるGSK3βの役割2015
Author(s)
堂本 貴寛, 紙 健次郎, 廣瀬 まゆみ, Ilya V. Pyko, 土原 一哉, 曽我 朋義, 江角 浩安, 源 利成
Organizer
第3回がんと代謝研究会
Place of Presentation
金沢市・県立音楽堂
Year and Date
2015-07-16 – 2015-07-17
Related Report
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[Presentation] Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1 and JNK-mediated pathway2015
Author(s)
Takahiro Domoto, Yuri Chikano, Takuya Furuta, Hemragul Sabit, Ilya V. Pyko, Takahisa Takino, Yutaka Hayashi, Hiroshi Sato, Mitsutoshi Nakada, Toshinari Minamoto
Organizer
日本癌学会主催 金沢大学がん進展制御研究所共催 日本癌学会シンポジウム共同利用・共同研究拠点シンポジウム
Place of Presentation
石川県立音楽堂(石川県・金沢市)
Year and Date
2015-01-22 – 2015-01-23
Related Report
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[Presentation] 大腸がんにおけるGSK3β制御性miRNAの発現と病態との関連2015
Author(s)
佐々木 規雄, 堂本 貴寛, 米村 圭祐, 森脇 美優, Ilia V. Pyko, 中村 慶史, 太田 哲夫, 河原 栄, 源 利成
Organizer
日本癌学会主催 金沢大学がん進展制御研究所共催 日本癌学会シンポジウム共同利用・共同研究拠点シンポジウム
Place of Presentation
石川県立音楽堂(石川県・金沢市)
Year and Date
2015-01-22 – 2015-01-23
Related Report
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