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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

Tumor suppression by cell competition through regulation of the Hippo pathway

Chiao-Lin Chen1, Molly C Schroeder, Madhuri Kango-Singh

  • 1Department of Biochemistry and Molecular Biology and Program in Genes and Development, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 23, 2011
PubMed

Insights

Cell competition prevents cancerous growth by regulating the Hippo pathway. This mechanism suppresses Yorkie (Yki) activity in abnormal cells, acting as a tumor suppressor.

Area of Science:

  • Cell biology
  • Developmental biology
  • Cancer research

Background:

  • Homeostatic mechanisms eliminate abnormal cells, preventing diseases like cancer.
  • The precise mechanisms of this cellular surveillance remain largely unknown.
  • Neoplastic tumor suppressor gene scribble (scrib) mutations can lead to uncontrolled cell growth.

Purpose of the Study:

  • To investigate how clones of scribble (scrib) mutant cells are eliminated from Drosophila imaginal discs.
  • To elucidate the role of cell competition in preventing overproliferation of scrib(-) cells.
  • To understand how the Hippo pathway is regulated during this process.

Main Methods:

  • Utilizing Drosophila imaginal discs as a model system.
  • Generating clones of cells mutant for the scribble gene.
  • Analyzing the activity of the Hippo pathway effector Yorkie (Yki).
  • Investigating JNK-dependent apoptosis mechanisms.

Main Results:

  • scrib(-) cells hyperactivate the Hippo pathway effector Yorkie (Yki) when alone, leading to neoplastic growth.
  • In the presence of wild-type cells, cell competition suppresses Yki activity in scrib(-) cells.
  • Suppression of Yki activity is crucial for eliminating scrib(-) clones via cell competition.
  • Elevated Yki activity in scrib(-) cells promotes neoplastic growth.

Conclusions:

  • Cell competition acts as a critical tumor-suppressing mechanism.
  • This process regulates the Hippo pathway, specifically controlling Yorkie (Yki) activity in mutant cells.
  • Understanding these mechanisms can provide insights into cancer prevention and therapy.

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