The role of activin combined with different gene mutations in colorectal cancer EMT

激活素联合不同基因突变在结直肠癌EMT中的作用

• 批准号: 21K15502
• 负责人: WANG DONG
• 金额: $ 3万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K15502/
• 关键词: activin; driver gene mutation; colorectal cancer; EMT

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.

激活素在正常和良性肿瘤中诱导细胞凋亡，但在恶性肿瘤中诱导EMT。然而，激活素功能转换的机制尚不清楚。在该项目中，使用携带多个驱动突变的小鼠肠道肿瘤衍生类器官来探索激活素的功能以及激活素改变其自身功能的机制。我们证实了激活素在具有各种组合突变的不同类器官中的功能。初步探讨了激活素诱导细胞凋亡的驱动基因kras的突变及其机制。同时，我们发现了激活素诱导EMT的调控因子p53功能获得性突变，阐明了激活素与p53功能获得性突变相互作用诱导EMT的机制。

项目成果

Nano-scale physical properties characteristic to intestinal cancer cells identified by high speed-scanning ion conductance microscope

高速扫描离子电导显微镜鉴定肠癌细胞的纳米级物理特性

• DOI: 10.1016/j.biomaterials.2021.121256
• 发表时间: 2022
• 期刊: Biomaterials
• 影响因子: 14
• 作者: D. Wang;L. Sun;S. Okuda;D. Yamamoto;M. Nakayama;H. Oshima;H. Saito;Y. Kouyama;K. Mimori;T. Ando;S. Watanabe;M. Oshima
• 通讯作者: M. Oshima

Activin promotes intestinal tumor cell metastasis by interacting with gain-of-function mutant p53

激活素通过与功能获得突变体 p53 相互作用促进肠道肿瘤细胞转移

• 发表时间: 2022
• 作者: Dong Wang;Mizuho Nakayama;Hiroko Oshima;Masanobu Oshima
• 通讯作者: Masanobu Oshima