Peritumoral activation of the Hippo pathway effectors YAP and TAZ suppresses liver cancer in mice
- 21 November 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 366 (6468), 1029-1034
- https://doi.org/10.1126/science.aaw9886
Abstract
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.Keywords
Funding Information
- Cancer Prevention and Research Institute of Texas (RP180530)
- European Research Council (724226_cis-CONTROL)
- Fonds Wetenschappelijk Onderzoek (G030616N)
- Fonds Wetenschappelijk Onderzoek (G0C2418N)
- Stichting Tegen Kanker (FAF-F/2016/867)
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