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Updated: Apr 6, 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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Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway

Nam-Gyun Kim1, Barry M Gumbiner2

  • 1Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, VA 22908.

The Journal of Cell Biology
|July 29, 2015
PubMed

Insights

Fibronectin adhesion activates focal adhesion kinase (FAK)-Src signaling, negatively regulating the Hippo pathway. This pathway controls Yes-associated protein (YAP) nuclear accumulation, impacting cell proliferation and responses to stimuli.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Hippo pathway regulates cell proliferation and organ size.
  • Upstream regulators like EGF ligands and LPA are known.
  • Contact inhibition is a key function of the Hippo pathway.

Purpose of the Study:

  • To identify novel upstream regulators of the Hippo pathway.
  • To investigate the role of fibronectin adhesion in Hippo signaling.
  • To elucidate the mechanism of YAP nuclear localization.

Main Methods:

  • MCF-10A cell culture and adhesion assays.
  • Inhibition of FAK, Src, PI3K, and PDK1 signaling.
  • Western blotting and immunofluorescence for YAP localization.

Main Results:

  • Fibronectin adhesion activates FAK-Src signaling, a negative regulator of the Hippo pathway.
  • FAK/Src inhibition prevents YAP activation in a Lats-dependent manner.
  • YAP nuclear accumulation upon fibronectin adhesion is mediated by FAK-Src-PI3K signaling.

Conclusions:

  • Fibronectin adhesion signaling negatively regulates the Hippo pathway.
  • This mechanism explains cell spreading effects on YAP localization.
  • It highlights a Lats-dependent response to cell adhesion.

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