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Updated: Feb 8, 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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Assembly and activation of the Hippo signalome by FAT1 tumor suppressor

Daniel Martin1, Maria S Degese1, Lynn Vitale-Cross1

  • 1Oral and Pharyngeal Cancer Branch, National Institutes of Health, Bethesda, MD 20892, USA.

Nature Communications
|July 10, 2018
PubMed

Insights

Loss of FAT1 function in head and neck squamous cell carcinoma (HNSCC) activates YAP1. This discovery reveals FAT1

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The Hippo signaling pathway regulates organ size and is frequently dysregulated in cancer.
  • YAP1 activation, a consequence of Hippo pathway dysregulation, drives tumorigenesis.
  • Molecular mechanisms linking Hippo pathway alterations to cancer remain incompletely understood.

Purpose of the Study:

  • To investigate the role of FAT1 in Hippo signaling and YAP1 activation in human malignancies.
  • To elucidate the functional consequences of FAT1 alterations in head and neck squamous cell carcinoma (HNSCC).
  • To explore YAP1 as a potential therapeutic target in FAT1-altered cancers.

Main Methods:

  • Pancancer analysis of Hippo pathway kinases and regulatory molecules.
  • Focus on genetic alterations in the FAT family, particularly FAT1, in HNSCC.
  • Functional studies to link FAT1 loss to YAP1 activation and oncogenic functions.

Main Results:

  • Few alterations found in canonical Hippo pathway components across cancers.
  • Frequent genetic alterations identified in FAT atypical cadherins.
  • FAT1 functional loss in HNSCC leads to YAP1 activation.
  • FAT1 assembles a Hippo signaling complex, activating TAOKs and inactivating YAP1.
  • Unrestrained YAP1 drives HNSCC oncogenesis.

Conclusions:

  • FAT1 acts as a tumor suppressor by maintaining Hippo pathway integrity.
  • YAP1 is a critical oncogenic driver in HNSCC with FAT1 alterations.
  • Targeting YAP1 offers a potential precision therapeutic strategy for FAT1-mutated cancers.

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