Bile Acids Activate YAP to Promote Liver Carcinogenesis

Sayeepriyadarshini Anakk, Manoj Bhosale, Valentina A. Schmidt, Randy L. Johnson, Milton J. Finegold, David D. Moore

Research output: Contribution to journalArticlepeer-review

Abstract

Elevated bile acid levels increase hepatocellular carcinoma by unknown mechanisms. Here, we show that mice with a severe defect in bile acid homeostasis due to the loss of the nuclear receptors FXR and SHP have enlarged livers, progenitor cell proliferation, and Yes-associated protein (YAP) activation and develop spontaneous liver tumorigenesis. This phenotype mirrors mice with loss of hippo kinases or overexpression of their downstream target, YAP. Bile acids act as upstream regulators of YAP via a pathway dependent on the induction of the scaffold protein IQGAP1. Patients with diverse biliary dysfunctions exhibit enhanced IQGAP1 and nuclear YAP expression. Our findings reveal an unexpected mechanism for bile acid regulation of liver growth and tumorigenesis via the Hippo pathway.

Original languageEnglish (US)
Pages (from-to)1060-1069
Number of pages10
JournalCell Reports
Volume5
Issue number4
DOIs
StatePublished - Nov 27 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Bile Acids Activate YAP to Promote Liver Carcinogenesis'. Together they form a unique fingerprint.

Cite this