Gene expression change of MDCK cells expressing scribble shRNA in a tetracycline-inducible manner (scribKD cells)

Cell competition is a social cellular phenomenon in which unfit cells are selectively eliminated by wild-type (WT) cells. Although recent studies show that mechanical forces induce competitive cell-cell interactions, it remains largely unknown how unfit cells are sensed and mechanically eliminated. Here, we report that MDCK cells depleted of the polarity gene scribble (scribKD cells) secrete FGF21 to drive cell competition. Knockdown of FGF21 in scribKD cells or loss of FGFR1 in WT cells increases the survival rate of scribKD cells in cell competition, suggesting that WT cells recognize scribKD cells through FGF21. Moreover, FGF21 promotes the compression and elimination of scribKD cells by attracting surrounding WT cells. We also demonstrate that activation of the ASK1-p38 pathway in scribKD cells induces FGF21 to drive cell competition. Our findings reveal a mechanism whereby WT cells mechanically eliminate scribKD cells and propose a new function for FGF21 in cell-cell communication. We performed DNA microarray analysis to search for the genes responsible for cell competition. mRNA of scribKD cells were extracted at 30, 45 and 60 hours after treatment with or without tetracycline (Tet).