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

Epithelial cells expressing oncogenic Ras (RasV12) are detected by normal neighbors and are often extruded from tissues. We recently demonstrated that differential EphA2 signaling drives the segregation of mutant cells from normal monolayers via cell repulsion and increased RasV12 cell contractility. EphA2 signaling on RasV12 cells is triggered by ephrin-A ligands presented by normal cells. Here, we show that normal epithelial cells trigger the repulsion and enhanced contractility of Ras-transformed epithelial cells at the single cell level. We also reveal that ephrin-A ligands expressed on RasV12 cells are not required to drive RasV12 cell segregation following interaction with normal cells. Thus, normal-RasV12 cell-cell interaction triggers EphA2 forward signaling in RasV12 cells to drive repulsion and segregation of the transformed cells.