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Updated: Feb 25, 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

20.8K

Src Inhibits the Hippo Tumor Suppressor Pathway through Tyrosine Phosphorylation of Lats1

Yuan Si1, Xinyan Ji1, Xiaolei Cao1

  • 1Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China.

Cancer Research
|July 30, 2017
PubMed

Insights

The Src kinase phosphorylates LATS1, a tumor suppressor, impacting the Hippo pathway. This regulates YAP, a key factor in cell growth, and contributes to cancer development.

Area of Science:

  • Cell biology
  • Molecular oncology
  • Signal transduction

Background:

  • The Hippo pathway is crucial for organ size control, regulating cell proliferation and apoptosis.
  • Deregulation of the Hippo pathway is implicated in human cancers, but mechanisms remain unclear.
  • Cell adhesion influences Hippo pathway activity, but the precise molecular links are not fully elucidated.

Purpose of the Study:

  • To investigate the molecular mechanisms linking cell adhesion to Hippo pathway regulation.
  • To identify kinases that phosphorylate LATS1, a key tumor suppressor in the Hippo pathway.
  • To understand the role of Src-mediated LATS1 phosphorylation in tumorigenesis and YAP activation.

Main Methods:

  • Tyrosine kinase library screening to identify LATS1-interacting kinases.
  • In vitro kinase assays to confirm Src-mediated phosphorylation of LATS1.
  • Analysis of LATS1 structure, Mob kinase binding, and YAP activity.
  • Correlation studies in human breast cancer tissues.

Main Results:

  • Src was identified as a direct tyrosine kinase phosphorylating LATS1.
  • Src-mediated LATS1 phosphorylation inhibits its binding to Mob kinase and alters its substrate-binding pocket.
  • Cell adhesion activates YAP via Src-mediated LATS1 inhibition.
  • Aberrant Src activation promotes tumorigenesis in a YAP-dependent manner.
  • Src levels correlate with active YAP in human breast cancers.

Conclusions:

  • Tyrosine phosphorylation of LATS1 by Src is a novel mechanism regulating the Hippo pathway in response to cell adhesion.
  • Src activation contributes to YAP deregulation and tumorigenesis in cancers.
  • This study reveals a new link between cell adhesion, Src signaling, and the Hippo pathway in cancer development.

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