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NUAK2 is a critical YAP target in liver cancer

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Listed:
  • Wei-Chien Yuan

    (Boston Children’s Hospital
    Harvard University
    Harvard Stem Cell Institute)

  • Brian Pepe-Mooney

    (Boston Children’s Hospital
    Harvard University)

  • Giorgio G. Galli

    (Boston Children’s Hospital
    Harvard University
    Harvard Stem Cell Institute
    Disease Area Oncology)

  • Michael T. Dill

    (Boston Children’s Hospital
    Harvard University
    Harvard Stem Cell Institute)

  • Hai-Tsang Huang

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Mingfeng Hao

    (Harvard Medical School)

  • Yumeng Wang

    (The University of Texas MD Anderson Cancer Center)

  • Han Liang

    (The University of Texas MD Anderson Cancer Center)

  • Raffaele A. Calogero

    (University of Torino)

  • Fernando D. Camargo

    (Boston Children’s Hospital
    Harvard University
    Harvard Stem Cell Institute)

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.

Suggested Citation

  • 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, 2018. "NUAK2 is a critical YAP target in liver cancer," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07394-5
    DOI: 10.1038/s41467-018-07394-5
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