期刊
SCIENCE
卷 366, 期 6468, 页码 1029-1034出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaw9886
关键词
-
资金
- Research Foundation Flanders (FWO)
- FWO
- German Research Foundation [DFG EXC 2180 - 390900677, FOR2314, SFB-TR209]
- German Ministry for Education and Research (BMBF)
- European Research Council
- German Center for Translational Cancer Research (DKTK)
- Stichting tegen Kanker [FAF-F/2016/867]
The Hippo signaling pathway and its two downstream effectors, the YAP and TAZ transcriptional coactivators, are drivers of tumor growth in experimental models. Studying mouse models, we show that YAP and TAZ can also exert a tumor-suppressive function. We found that normal hepatocytes surrounding liver tumors displayed activation of YAP and TAZ and that deletion of Yap and Taz in these peritumoral hepatocytes accelerated tumor growth. Conversely, experimental hyperactivation of YAP in peritumoral hepatocytes triggered regression of primary liver tumors and melanoma-derived liver metastases. Furthermore, whereas tumor cells growing in wild-type livers required YAP and TAZ for their survival, those surrounded by Yap- and Taz-deficient hepatocytes were not dependent on YAP and TAZ. Tumor cell survival thus depends on the relative activity of YAP and TAZ in tumor cells and their surrounding tissue, suggesting that YAP and TAZ act through a mechanism of cell competition to eliminate tumor cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据