YTHDF1 Amplifies Wnt/β-Catenin Signaling to Promote Intestinal Stemness
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
下载链接：
http://data.iscr.ac.cn/Article?id=51fc2be0a6293959168257b3bf2dc437
下载链接
链接失效反馈官方服务：
资源简介：
Wnt/β-catenin signaling is essential for intestinal stem cell homeostasis and aberrant activation of this signaling leads to tumorigenesis. Here we report a function of YTHDF1, an mRNA m6A reader, in mediating β-catenin hyperactivation. Wnt signaling promotes YTHDF1 expression at the translational level. YTHDF1 is dispensable for normal intestinal development in mice while essential for intestinal regeneration. Ythdf1 knockout reduces the stemness of intestinal stem cells, which blocks Wnt-driven tumorigenesis. Genome-wide analysis identifies a subset of Wnt signaling components regulated by YTHDF1 in an m6A-dependent manner. Moreover, we demonstrate that YTHDF1 promotes the translation of TCF7L2/TCF4 to augment β-catenin activation. Targeting YTHDF1 in the established tumors leads to tumor shrinkage and prolonged survival. Together, our studies uncover YTHDF1 as an integral regulator of Wnt signaling at the translational level during intestinal tumorigenesis, which might serve as a promising target for colorectal cancer therapy.
提供机构：
Cornell University
创建时间：
2022-02-20
