Related Experiment Video

Updated: Feb 6, 2026

De Novo Generation of Somatic Stem Cells by YAP/TAZ
13:05

De Novo Generation of Somatic Stem Cells by YAP/TAZ

Published on: May 7, 2018

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A feed forward loop enforces YAP/TAZ signaling during tumorigenesis

Mandeep K Gill1,2, Tania Christova1,2, Ying Y Zhang3,4

  • 1Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.

Nature Communications
|August 31, 2018
PubMed

Insights

Researchers discovered NUAK2 activates YAP/TAZ signaling, promoting cancer growth. Inhibiting NUAK2 slowed tumor growth in mice, suggesting NUAK2 as a potential cancer therapeutic target for reactivating the Hippo pathway.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The Hippo pathway regulates organ size and is often inactivated in solid tumors.
  • Yeast and TAZ (transcriptional co-activators) are key downstream effectors of the Hippo pathway.
  • Mechanisms of Hippo pathway inactivation and YAP/TAZ activation in cancer are not fully understood.

Purpose of the Study:

  • To identify novel regulators of YAP/TAZ activity in cancer.
  • To investigate the role of NUAK2 in Hippo pathway signaling and tumor progression.
  • To explore NUAK2 as a potential therapeutic target for YAP/TAZ-driven cancers.

Main Methods:

  • Investigated NUAK2's interaction with YAP/TAZ and LATS kinase.
  • Assessed the impact of NUAK2 inhibition on cancer cell growth and mammary tumor development in mouse models.
  • Analyzed NUAK2 expression and its correlation with YAP/TAZ signatures in human bladder cancer patient samples.

Main Results:

  • NUAK2 was identified as a direct activator of YAP/TAZ by inhibiting LATS-mediated phosphorylation.
  • NUAK2 expression is induced by YAP/TAZ and AP-1, forming a positive feedback loop.
  • Pharmacological inhibition or genetic loss of NUAK2 suppressed cancer cell proliferation and mammary tumor growth in vivo.
  • Elevated NUAK2 expression in aggressive bladder cancer correlated strongly with YAP/TAZ gene signatures.

Conclusions:

  • NUAK2 plays a critical role in sustaining YAP/TAZ signaling and promoting tumor growth.
  • A positive feedback loop involving NUAK2, YAP/TAZ, and AP-1 reinforces oncogenic signaling.
  • NUAK2 represents a promising therapeutic target for reactivating the Hippo pathway in YAP/TAZ-driven cancers.

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