雅普1
河马信号通路
生物
癌变
转录因子
癌基因
癌症研究
细胞生物学
效应器
细胞生长
细胞
细胞周期
癌症
基因
遗传学
作者
Miju Kim,Seav Huong Ly,Yingtian Xie,Gina N. Duronio,Dane Ford-Roshon,Justin Hwang,Rita Sulahian,Jonathan Rennhack,Jonathan So,Ole Gjoerup,Jessica A. Talamas,Maximilien Grandclaudon,Henry W. Long,John G. Doench,Nilay Sethi,Marios Giannakis,William C. Hahn
标识
DOI:10.1016/j.devcel.2021.12.006
摘要
The transcriptional co-activator YAP1 oncogene is the downstream effector of the Hippo pathway, which regulates tissue homeostasis, organ size, regeneration, and tumorigenesis. Multiple cancers are dependent on sustained expression of YAP1 for cell proliferation, survival, and tumorigenesis, but the molecular basis of this oncogene dependency is not well understood. To identify genes that can functionally substitute for YAP1, we performed a genome-scale genetic rescue screen in YAP1-dependent colon cancer cells expressing an inducible YAP1-specific shRNA. We found that the transcription factor PRDM14 rescued cell proliferation and tumorigenesis upon YAP1 suppression in YAP1-dependent cells, xenografts, and colon cancer organoids. YAP1 and PRDM14 individually activated the transcription of calmodulin 2 (CALM2) and a glucose transporter SLC2A1 upon YAP1 suppression, and CALM2 or SLC2A1 expression was required for the rescue of YAP1 suppression. Together, these findings implicate PRDM14-mediated transcriptional upregulation of CALM2 and SLC2A1 as key components of oncogenic YAP1 signaling and dependency.
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