Yuan WC, Pepe-Mooney B, Galli GG, Dill MT, Huang HT, Hao M, Wang Y, Liang H, Calogero RA, Camargo FD. 2018. NUAK2 is a critical YAP target in liver cancer. Nature communications. 9(1):4834. Pubmed: 30446657 DOI:10.1038/s41467-018-07394-5


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.

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The Camargo laboratory focuses on the study of adult stem cell biology, organ size regulation, and cancer.

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