EPLIN is a crucial regulator for extrusion of RasV12-transformed cells

Abstract

At the initial stage of carcinogenesis, a mutation occurs in a single cell within a normal epithelial layer. We have previously shown that RasV12-transformed cells are apically extruded from the epithelium when surrounded by normal cells. However, the molecular mechanisms underlying this phenomenon remain elusive. Here, we demonstrate that Cav-1-containing microdomains and EPLIN are accumulated in RasV12-transformed cells that are surrounded by normal cells. We also show that knockdown of Cav-1 or EPLIN suppresses apical extrusion of RasV12-transformed cells, suggesting their positive role in the elimination of transformed cells from epithelia. EPLIN functions upstream of Cav-1 and affects its enrichment in RasV12-transformed cells that are surrounded by normal cells. Furthermore, EPLIN regulates non-cell autonomous activation of myosin-II and PKA in RasV12-transformed cells. In addition, EPLIN substantially affects accumulation of filamin A, a vital player in EDAC (Epithelial Defense Against Cancer), in the neighboring normal cells, and vice versa. These results indicate that EPLIN is a crucial regulator for the interaction between normal and transformed epithelial cells.