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

激活素在正常和良性肿瘤中诱导细胞凋亡，而在恶性肿瘤中诱导EMT。然而，激活素功能转换的机制尚不清楚。在本项目中，携带多个驱动突变的小鼠肠道肿瘤衍生的有机化合物被用来探索激活素的功能以及激活素改变自身功能的机制。我们证实了激活素在具有不同组合突变的不同有机化合物中的功能。我们认为，驱动基因突变KRAS在激活素诱导的细胞凋亡及其机制中起着重要作用。同时，我们找到了激活素诱导EMT的调控因子--P53功能突变增益，阐明了激活素与P53功能突变增益相互作用的机制。

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.