| 研究実績の概要 |
In this project, we investigated the role and mechanism of activin in malignant progression of colorectal cancer. In FY2021, I treated the mouse intestine tumor derived organoids with different combination of driver gene mutations with activn. We found that organoids with the Kras mutation were able to survive after activin stimulation, whereas activin induces growth suppression in organoids without the Kras mutation, indicating that the Kras activation mutation protects cells from activin-induced growth suppression. Importantly, we found that activin induces protrusion of organoids and promotes lung metastasis in p53 mutation-dependent manner. All of these results indicated that the background genetic alterations play an important role in activin-induced metastasis.
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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
As TGF-β induces apoptosis in normal cells and promotes EMT in malignant cancer cells; activin shares the same downstream genes with TGF-β; accumulation of key driver gene mutations causes gradual acquisition of malignant phenotypes. Accordingly, we make a hypothesis that simple or certain combined genetic alterations in driver genes may change the cell characteristics in response to activin. In our results, we found two driver mutations control the response to activin that Kras mutation inhibits activin-induced cell proliferation arrest; p53 mutation interacts with activin to induce metastasis. These results confirmed that driver gene mutations play an important role in activin-induced malignant progression.
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