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Updated: Jan 23, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

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

Published on: September 13, 2018

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Hippo kinases regulate cell junctions to inhibit tumor metastasis in response to oxidative stress

Yang Wang1, Juan Li1, Ya Gao1

  • 1Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China.

Redox Biology
|June 19, 2019
PubMed

Insights

Oxidative stress suppresses tumor metastasis by activating Hippo kinase MST1/2, which regulates cell adhesion and migration. This pathway, involving FoxO3a and ΔNp63α, is crucial for controlling cancer spread.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Reactive oxygen species (ROS) are vital in cancer development but their role in tumor metastasis remains unclear.
  • Understanding ROS's impact on metastasis is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the role of oxidative stress and the Hippo kinase pathway in regulating tumor metastasis.
  • To elucidate the specific functions of MST1 and MST2 in cell adhesion, migration, and metastasis.

Main Methods:

  • Investigated the effects of oxidative stress on tumor metastasis in cellular and molecular models.
  • Analyzed the activation of the Hippo kinase pathway, including MST1/2, FoxO3a, and YAP.
  • Examined the expression of key adhesion molecules like E-cadherin and integrin β4.
  • Assessed the impact of MST1 and MST2 loss on cell behavior and tumor metastasis.
  • Correlated MST1/2 expression with human breast carcinoma samples.

Main Results:

  • Oxidative stress inhibited tumor metastasis through MST1/2 activation, leading to FoxO3a phosphorylation and nuclear accumulation.
  • MST1 loss disrupted cell-cell junctions (reduced E-cadherin), while MST2 loss impaired cell-matrix adhesion (reduced integrin β4), increasing migration.
  • MST1 and MST2 expression were downregulated in human breast carcinoma.
  • The MST2-FoxO3a-ΔNp63α pathway mediated oxidative stress's inhibition of HER2- or PI3K-driven metastasis.

Conclusions:

  • A noncanonical Hippo pathway (MST2-FoxO3a-ΔNp63α) is critical for ROS-mediated regulation of cell migration and tumor metastasis.
  • Differential roles of MST1 and MST2 in cell adhesion and migration highlight their importance in metastasis.
  • Targeting this pathway could offer novel therapeutic strategies for preventing cancer metastasis.
Keywords:
Cell-cell junctionCell-matrix adhesionHippo kinaseMetastasisΔNp63α

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