Cell competition: emerging signaling and unsolved questions

Cell competition is a form of cell –cell interaction whereby cells with higher fitness (“winners”) actively eliminate neighboring less-fit cells (“losers”) in the growing tissue. In this review, we summarize and discuss emerging signaling mechanisms and critical unsolved questions in cell competition. Multicellular communities have an intrinsic mechanism that optimizes their structure and functionvia cell –cell communication. One of the driving forces for such self-organization of the multicellular system is cell competition, the elimination of viable unfit or deleterious cellsvia cell –cell interaction. Studies inDrosophila and mammals have identified multiple mechanisms of cell competition caused by different types of mutations or cellular changes. Intriguingly, recent studies have found that different types of “losers” of cell competition commonly show reduced protein synthesis. InDrosophila, the reduction in protein synthesis levels in loser cells is caused by phosphorylation of the translation initiation factor eIF2 αvia a bZip transcription factor Xrp1. Given that a variety of cellular stresses converge on eIF2 α phosphorylation and thus global inhibition of protein synthesis, cell competition may be a machinery that optimizes multicellular fitness by removing stressed cells. In this review, we summarize and discuss emerging signaling mechanisms and critical unsolved questions, as well as the role of prot ein synthesis in cell competition.

Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Rina Nagata, Tatsushi Igaki Tags: Review Source Type: research