Exploring biological basis of aberrant cancer energy metabolism induced by GSK3beta toward application to cancer treatment
| Project/Area Number |
17K15022
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | Kanazawa University |
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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
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 分子標的治療 / がん代謝 / GSK3β / オートファジー / リン酸化 |
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| Outline of Final Research Achievements |
We investigated the tumor-promoting mechanisms induced by GSK3β on energy metabolism including Warburg effect and autophagy. Aberrant GSK3β enhanced glycolysis, and led autophagic activation by induction of expression of autophagy-related transcription factors in colon cancer cells. Combined treatment with specific GSK3β inhibitor (AR-A014418) and autophagy inhibitor (hydroxychloroquine) synergistically suppressed proliferation of cancer cells. These results suggest that GSK3β is attractive candidate for cancer energy metabolism targeted therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
がんの主要エネルギー源である解糖系とオートファジーをGSK3βが統合的に制御していることが示され、GSK3β阻害によって、がん特有の代謝を一括で標的にするという独創的な治療法開発の科学的基盤になることが期待される。また、GSK3βは多彩な細胞機能を制御し、ひろく疾患に関与している。したがって、本研究の成果はがんの病態解明や医療応用に繋がることはもとより、近接領域の細胞現象への理解や他の疾患に関する治療への応用に波及する可能性がある。
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Report
(3 results)
Research Products
(22 results)
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[Presentation] Novel molecular therapy targeting aberrant glycogen synthase kinase-3β in soft tissue sarcoma: a basic research2018
Author(s)
Kensaku Abe, Norio Yamamoto, Takahiro Domoto, Katsuhiro Hayashi, Akihiko Takeuchi, Kentaro Igarashi, Yuta Taniguchi, Hirotaka Yonezawa, Yoshihiro Araki, Toshinari Minamoto, Hiroyuki Tsuchiya
Organizer
19th EFORT Annual Congress Barcelona 2018
Related Report
Int'l Joint Research
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