| Project/Area Number |
18K07239
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 50010:Tumor biology-related
|
|---|
| Research Institution | Kagoshima University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
|
|---|
| Keywords | ROS / ABCB10 / Ros / TIC / 活性酸素 / tumor-initiating cells / 鉄 / 代謝 |
|---|
| Outline of Final Research Achievements |
The reprogramming of iron and ROS(reactive oxygen species) metabolism is important matter for canceration and survival in tumor cells. However, the major factor for regulating the reprogramming is unproved. The functional analysis of Abcb10 (ATP binding cassette sub-family B10) that localized in mitochondrial inner membrane showed that Abcb10 is essential for Heme-biosynthesis and the myeloid cells lacking Abcb10 accumulate the Heme precursors both of PPIX and iron and undergo ROS mediated cell death. The purpose of research is to examine that the abundance iron-accumulation by the loss and change in Abcb10 expression whether induce the reprogramming of iron metabolism and influence on development, malignancy and drug-sensitive of tumor-cells.
|
| Academic Significance and Societal Importance of the Research Achievements |
ABCB10の発現変化はThe Cancer Genome Atlas（TCGA）を用いた解析において肺がん、乳がん、膀胱がん患者の生存期間に有意差を認めるが発現比は微細であり、ABCB10が予後因子であることを判断することは難しい。一方、in vitroにおいてTICから分化した通常細胞との間における遺伝子発現変化を比較・解析する方法は、その表現形質を明確に分けて解析することを可能としており、腫瘍環境に依存したROSの代謝経路のリプログラミングにABCB10が関与すること、およびリプログラミングを受ける因子を明らかにすることで、腫瘍に対する特異的かつ効果的な治療薬の創薬が期待できると考えた。
|
