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Updated: Jun 25, 2025

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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A connection between phosphatidylinositol 5-phosphate and the Hippo pathway to prevent epithelial-mesenchymal

Emilio Hirsch1, Emanuele Fantastico1, Lorenzo Prever1

  • 1Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10125 Torino Italy.

Science Signaling
|May 28, 2024
PubMed

Insights

Phosphatidylinositol 5-phosphate (PI5P) boosts the Hippo pathway, a key regulator of cancer metastasis. The Hippo pathway then creates a feedback loop, preventing PI5P conversion into PIP2, thus controlling cancer progression.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Signaling

Background:

  • The Hippo pathway is a critical regulator of organ size and tumor suppression.
  • Yeast And Protein (YAP) is a transcriptional coactivator that promotes cell proliferation and metastasis when the Hippo pathway is inactivated.
  • Epithelial-mesenchymal transition (EMT) is a process crucial for cancer metastasis.

Purpose of the Study:

  • To investigate the role of phosphatidylinositol 5-phosphate (PI5P) in Hippo pathway regulation.
  • To elucidate the interplay between PI5P, the Hippo pathway, and cancer metastasis.
  • To identify potential therapeutic targets for cancer treatment by understanding this signaling axis.

Main Methods:

  • Cell-based assays to measure Hippo pathway activity.
  • Biochemical experiments to analyze lipid metabolism and protein interactions.
  • Analysis of gene expression related to EMT and metastasis.

Main Results:

  • Phosphatidylinositol 5-phosphate (PI5P) was found to enhance Hippo pathway activation.
  • The Hippo pathway was shown to inhibit the conversion of PI5P into phosphatidylinositol 4,5-bisphosphate (PIP2).
  • This creates a positive feedback loop that reinforces Hippo pathway signaling and potentially suppresses metastasis.

Conclusions:

  • PI5P plays a crucial role in promoting Hippo pathway activity.
  • The Hippo pathway-mediated inhibition of PI5P to PIP2 conversion represents a novel feedback mechanism.
  • Targeting this PI5P-mediated feedback loop could offer new therapeutic strategies against YAP-driven cancers.

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