2018 Fiscal Year Final Research Report
Exploring biological basis of aberrant cancer energy metabolism induced by GSK3beta toward application to cancer treatment
| Project/Area Number |
17K15022
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Tumor therapeutics
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
DOMOTO TAKAHIRO 金沢大学, がん進展制御研究所, 助教 (80635540)
|
|---|
| Research Collaborator |
MINAMOTO toshinari
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Keywords | 分子標的治療 / がん代謝 / GSK3β |
|---|
| 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.
|
| Free Research Field |
分子腫瘍学 腫瘍生物学
|
| 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。
|
