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Updated: Feb 23, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

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Mapping the STK4/Hippo signaling network in prostate cancer cell

Damien Ready1, Kader Yagiz2, Pooneh Amin3

  • 1Department of Mathematics, Statistics, and Computer Science, Marquette University, Milwaukee, Wisconsin, United States of America.

Plos One
|September 8, 2017
PubMed

Insights

The Hippo-YAP pathway kinase STK4 restricts aggressive prostate cancer growth. Nuclear and lipid raft STK4 show stronger suppressive effects on cell growth and gene expression than cytoplasmic STK4.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Dysregulation of the MST1/STK4 kinase, a core component of the Hippo-YAP pathway, is implicated in aggressive cancers with poor prognoses.
  • The precise mechanisms by which STK4 inhibits aggressive cancer development are not fully understood.

Purpose of the Study:

  • To investigate the impact of STK4 localization (cytoplasmic, lipid raft, nuclear) on cell growth and gene expression in aggressive prostate cancer.
  • To elucidate how STK4's subcellular positioning influences its tumor-suppressive functions.

Main Methods:

  • Utilized RNA sequencing and bioinformatics analysis to identify differentially expressed genes in response to ectopic STK4 expression across different cellular compartments.
  • Conducted in vitro and in vivo experiments to assess the effects of STK4 on aggressive prostate cancer cell growth.

Main Results:

  • Lipid raft and nuclear STK4 exhibited significantly greater suppressive effects on cell growth compared to cytoplasmic STK4.
  • Ectopic STK4 influenced gene expression across all three compartments, with lipid raft and nuclear localization affecting a larger number of genes.
  • Differentially expressed genes were associated with key oncogenic pathways including AR, PI3K/AKT, BMP/SMAD, GPCR, WNT, and RAS. Nuclear STK4 uniquely modulated the JAK/STAT pathway.

Conclusions:

  • MST1/STK4/Hippo signaling acts as a crucial suppressor of aggressive tumor cell proliferation by interacting with diverse molecular pathways.
  • Targeting the STK4/Hippo pathway holds potential therapeutic implications for managing aggressive cancers.

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