2018 Fiscal Year Final Research Report
Epigenetic regulation of iron trafficking in glioblastoma
| Project/Area Number |
17K15672
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Tokyo Women's Medical University |
|---|
Principal Investigator |
Masui Kenta 東京女子医科大学, 医学部, 助教 (60747682)
|
|---|
| Research Collaborator |
MISCHEL Paul
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Keywords | 悪性脳腫瘍 / mTOR複合体 / エピジェネティクス / ヒストンアセチル化 / 中心炭素代謝 / 鉄代謝 |
|---|
| Outline of Final Research Achievements |
Aberrant growth factor receptor signaling remodels intracellular metabolism and global gene transcription to drive aggressive cancer growth, but the underlying mechanisms are not well understood. Here we show that in the highly malignant brain tumor glioblastoma (GBM), mammalian target of rapamycin complex 2 (mTORC2), a critical effector of the growth factor signaling system, links metabolic reprogramming and acetyl-CoA production with genome-wide alteration of histone acetylation. Integrated analyses in mouse models and human GBM samples demonstrate that mTORC2 regulates iron trafficking via histone H3 acetylation of the ferritin promoter, promoting tumor cell proliferation and survival. These results nominate mTORC2 as a critical epigenetic regulator of iron metabolism in cancer.
|
| Free Research Field |
神経病理学
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究は、悪性度が高く有効な治療法がない脳腫瘍である膠芽腫において、腫瘍細胞内の鉄代謝の制御機構に着目することで、新しい治療戦略の可能性を探索する独創的な試みである。細胞を使った基礎的な実験に加えて、実際のヒト脳腫瘍標本を用いる病理組織学的解析を行うことで、悪性脳腫瘍の病態に関わる鉄代謝という基礎的な分子メカニズムが、本研究により診断・治療を含む臨床応用まで視野に入れた形で解明されることが期待される。
|
