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Significance This study shows that an oncogenic mammary epithelial cell surrounded by normal cells can extrude basally in vivo and invade surrounding tissues without formation of a primary tumor. Here, we show that overexpression of the key polarity protein atypical protein kinase C ι (aPKCi) is sufficient for triggering basally oriented epithelial cell extrusion and early cell invasion into the mammary gland stroma. Moreover, we highlight the importance of the difference between the mechanical properties of aPKCi-overexpressing cells and those of the normal surrounding cells associated with the decrease of vinculin at the cell junction, which triggers cell segregation, the first step toward promoting and controlling the direction of cell extrusion.

aPKCi triggers basal extrusion of luminal mammary epithelial cells by tuning contractility and vinculin localization at cell junctions