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Normal epithelial cells trigger EphA2-dependent RasV12 cell repulsion at the single cell level

William Hill1, Catherine Hogan1

  • 1a European Cancer Stem Cell Research Institute, School of Biosciences , Cardiff University , Cardiff , UK.

Small Gtpases
|June 22, 2017
PubMed

Insights

Normal cells detect and extrude RasV12-mutant epithelial cells. This study reveals normal cell interactions trigger EphA2 forward signaling in RasV12 cells, driving repulsion and tissue segregation.

Area of Science:

  • Cell biology
  • Cancer research
  • Developmental biology

Background:

  • Oncogenic Ras (RasV12) expression in epithelial cells triggers detection by normal neighbors, leading to cell extrusion.
  • Previous work identified differential EphA2 signaling as a driver of RasV12 cell segregation through repulsion and increased contractility.

Purpose of the Study:

  • To investigate the single-cell level mechanisms of RasV12 cell segregation from normal epithelial cells.
  • To determine the role of ephrin-A ligands on RasV12 cells in this segregation process.

Main Methods:

  • Single-cell interaction assays between normal and RasV12-expressing epithelial cells.
  • Analysis of EphA2 signaling pathways and cell contractility.
  • Investigation of ligand-receptor interactions at the cell-cell interface.

Main Results:

  • Normal epithelial cells directly trigger repulsion and enhanced contractility of Ras-transformed epithelial cells at the single-cell level.
  • EphA2 forward signaling in RasV12 cells is sufficient to drive repulsion and segregation.
  • Ephrin-A ligands expressed on RasV12 cells are not essential for segregation upon interaction with normal cells.

Conclusions:

  • Normal-RasV12 cell interactions initiate EphA2 forward signaling within RasV12 cells.
  • This signaling cascade promotes cell repulsion and segregation of transformed cells from normal tissue.
  • The findings clarify the cell-autonomous mechanisms governing tumor suppression via cell extrusion.
Keywords:
EphA2RasV12cell repulsionepithelialextrusionsingle cell

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