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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Notch signaling activates Yorkie non-cell autonomously in Drosophila

Hillary K Graves1, Sarah E Woodfield, Chih-Chao Yang

  • 1Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Plos One
|June 9, 2012
PubMed

Insights

Neoplastic tumor cells induce nearby cells to resist apoptosis via Notch signaling, activating Yorkie and promoting tumor growth. This study reveals a new mechanism for non-cell autonomous cell survival.

Area of Science:

  • Cell biology
  • Developmental biology
  • Cancer research

Background:

  • Mutant cells can influence neighboring cells, a process known as non-cell autonomous signaling.
  • The Hippo signaling pathway, particularly its effector Yorkie, plays a crucial role in cell growth and survival.
  • Notch signaling is involved in various cellular processes, including cell fate determination and survival.

Purpose of the Study:

  • To investigate the mechanism by which neoplastic tumor cells promote the survival of surrounding normal cells.
  • To identify the signaling pathways involved in the non-cell autonomous induction of apoptosis resistance.

Main Methods:

  • Utilized Drosophila imaginal epithelia as a model system.
  • Studied the role of the vps25 gene mutation in non-cell autonomous signaling.
  • Investigated the involvement of Yorkie and Notch signaling pathways.

Main Results:

  • Cells mutant for vps25 non-cell autonomously induce Drosophila Inhibitor-of-Apoptosis-Protein-1 (DIAP-1) in neighboring cells.
  • This induction is mediated by the Hippo pathway effector Yorkie.
  • Notch signaling from vps25 mutant cells triggers Yorkie activity, leading to DIAP-1 expression and apoptosis resistance.

Conclusions:

  • Identified a novel mechanism where Notch signaling promotes non-cell autonomous cell survival.
  • Demonstrated that neoplastic tumor cells create a supportive microenvironment for tumor growth through this pathway.
  • Highlighted the interplay between endocytic pathways, Hippo signaling, and Notch signaling in cancer progression.

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