Peritumoral activation of the Hippo pathway effectors YAP and TAZ suppresses liver cancer in mice

Iván M. Moya, Stéphanie A. Castaldo, Laura van den Mooter, Soheil Soheily, Leticia Sansores-Garcia, Jelle Jacobs, Inge Mannaerts, Jun Xie, Elisabeth Verboven, Hanne Hillen, Ana Algueró-Nadal, Ruchan Karaman, Matthias van Haele, Weronika Kowalczyk, Maxime de Waegeneer, Stefaan Verhulst, Panagiotis Karras, Leen van Huffel, Lars Zender, Jean Christophe MarineTania Roskams, Randy Johnson, Stein Aerts, Leo A. van Grunsven, Georg Halder

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1029-1034
Number of pages6
JournalScience
Volume366
Issue number6468
DOIs
StatePublished - Nov 22 2019

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Peritumoral activation of the Hippo pathway effectors YAP and TAZ suppresses liver cancer in mice'. Together they form a unique fingerprint.

Cite this