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Updated: May 1, 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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Effects of mTOR Inhibitors on Components of the Salvador-Warts-Hippo Pathway

Jonathan Chiang1, Julian A Martinez-Agosto2

  • 1Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. jchiang@mednet.ucla.edu.

Cells
|April 9, 2014
PubMed

Insights

The mechanistic target of rapamycin (mTOR) pathway regulates the Hippo signaling pathway in a cell-type-specific manner, impacting key transcriptional regulators like TAZ and TEAD1. This suggests mTOR inhibitors could treat Hippo-signaling dependent tumors.

Area of Science:

  • Cell biology
  • Molecular signaling pathways
  • Cancer research

Background:

  • The Hippo-Salvador-Warts-Hippo (SWH) and mechanistic target of rapamycin (mTOR)/Akt/phosphatidylinositol 3-kinase (PI3K) pathways are crucial for cell growth, proliferation, and survival, controlling organ size.
  • Cross-talk between these pathways is implicated in various biological processes.

Purpose of the Study:

  • To investigate the role of MST kinases and Sterile 20-like kinases (STKs) in mediating cross-talk between the Hippo and mTOR pathways.
  • To determine how mTOR signaling influences Hippo pathway components like TAZ and TEAD1.

Main Methods:

  • Expression analysis of key pathway components in HepG2 and MCF7 cell lines.
  • Treatment with mTOR inhibitors (rapamycin) and Akt inhibitors.
  • Assessment of TAZ and TEAD1 levels and TAZ cellular localization.

Main Results:

  • Common expression of MST/STK family kinases and Hippo pathway components (except YAP1 in MCF7 cells) was observed.
  • mTOR inhibition differentially affected TAZ and TEAD1 levels in HepG2 and MCF7 cells, indicating cell-type-specific regulation.
  • mTORC1/2 and Akt inhibition altered TAZ cellular localization.

Conclusions:

  • The mTOR pathway regulates Hippo signaling at the level of TAZ and TEAD1 transcriptional regulators in a cell-specific manner.
  • These findings suggest a potential therapeutic role for mTOR inhibitors in managing Hippo-signaling dependent tumors.

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