2022 Fiscal Year Research-status Report
The role of activin combined with different gene mutations in colorectal cancer EMT
| Project/Area Number |
21K15502
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| Research Institution | Kanazawa University |
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Principal Investigator |
WANG DONG 金沢大学, ナノ生命科学研究所, 特任助教 (20842983)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | activin / driver gene mutation / colorectal cancer / EMT |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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