| 研究課題/領域番号 |
21K15502
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| 研究機関 | 金沢大学 |
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研究代表者 |
WANG DONG 金沢大学, ナノ生命科学研究所, 特任助教 (20842983)
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| 研究期間 (年度) |
2021-04-01 – 2024-03-31
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| キーワード | activin / driver gene mutation / colorectal cancer / EMT |
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| 研究実績の概要 |
Activin induces apoptosis in normal and benign tumors but induces EMT in malignant tumors. However, the mechanism of activin functional switching is unclear. In this project, mouse intestinal tumor-derived organoids carrying multiple driver mutations were used to explore activin’s functions and the mechanism by which activin changes its own function. We confirmed activin’s functions in different organoids with various combination mutations. And we figured out that the driver gene mutation, kras, plays an important role in activin-induce apoptosis and the mechanism. Meantime, we found the regulator of activin-induced EMT, p53 gain of function mutation and clarified the mechanism by which activin interacts with p53 gain of function mutation inducing EMT.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We make a hypothesis that simple or certain combined genetic alterations in driver genes may change the cell characteristics in response to activin. In this project, we plan to study what’s the role of activin in different stages of colorectal cancer and which key driver gene mutations interact with activin to convert the apoptosis-inducing effect of activin into a EMT-inducing effect. So far, we already clarified activin’s functions in different-stages tumor derived organoids. And we figured out that kras mutation and p53 gain of function mutation interact with activin to convert the apoptosis-inducing effect of activin into a EMT-inducing effect. Finally, we performed RNA-seq and revealed the mechanism by which driver gene mutations effect activin’s functions.
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| 今後の研究の推進方策 |
Since we have revealed the mechanism by which activin interacts with p53 gain of function mutation inducing EMT, the next step, we will perform in vivo study to further confirm our finding. Then, we will collect human colon cancer samples with different tumor stages to confirm our findings in human tumor. Then, we will generate kras and p53 mutated human tumor cells to confirm the mechanisms we found in mouse. Also, we will confirm which stroma cells in the tumor microenvironment secret activin to activate tumor cells.
Finally, we will prepare and submit the manuscript.
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