NUAK2 is a critical YAP target in liver cancer

Wei Chien Yuan, Brian Pepe-Mooney, Giorgio G. Galli, Michael T. Dill, Hai Tsang Huang, Mingfeng Hao, Yumeng Wang, Han Liang, Raffaele A. Calogero, Fernando D. Camargo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

The Hippo-YAP signaling pathway is a critical regulator of proliferation, apoptosis, and cell fate. The main downstream effector of this pathway, YAP, has been shown to be misregulated in human cancer and has emerged as an attractive target for therapeutics. A significant insufficiency in our understanding of the pathway is the identity of transcriptional targets of YAP that drive its potent growth phenotypes. Here, using liver cancer as a model, we identify NUAK2 as an essential mediator of YAP-driven hepatomegaly and tumorigenesis in vivo. By evaluating several human cancer cell lines we determine that NUAK2 is selectively required for YAP-driven growth. Mechanistically, we found that NUAK2 participates in a feedback loop to maximize YAP activity via promotion of actin polymerization and myosin activity. Additionally, pharmacological inactivation of NUAK2 suppresses YAP-dependent cancer cell proliferation and liver overgrowth. Importantly, our work here identifies a specific, potent, and actionable target for YAP-driven malignancies.

Original languageEnglish
Article number4834
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018

Fingerprint

Dive into the research topics of 'NUAK2 is a critical YAP target in liver cancer'. Together they form a unique fingerprint.

Cite this