Cell Competition: Mechanisms and Physiological Roles

Abstract

Cell-competitive interactions are widespread in nature and determine the outcome of a vast variety of biological processes. A particular class of competitive interactions takes place when alterations in intrinsic cellular properties are sensed nonautonomously by comparison between neighboring cells, resulting in the selective elimination of one cell population. This type of cell competition was first described four decades ago in developing epithelia of Drosophila. In the last 15 years, further molecular and cellular analyses have provided essential knowledge about the mechanisms, universality, and physiological relevance of cell competition. The two main phenomena triggering cell competition are alterations in cellular metabolic status and alterations in epithelial apico-basal polarity, while other reported pathways are less characterized. Cell competition plays essential roles in quality control, homeostasis, and repair of developing and adult tissues, and depending on the context, it may function as a tumor-suppressing or tumor-promoting mechanism.

Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis

“…Cell competition is a conserved cell-elimination mechanism that functions through short-range cell-cell interactions whereby “winner” cells eliminate neighboring “loser” cells defective in some capacity, such as protein biogenesis, growth potential, or aberrant polarity (Amoyel and Bach, 2014; Baker, 2017; Claveria and Torres, 2016; de Beco et al, 2012; Maruyama and Fujita, 2017; Merino et al, 2016; Morata and Ballesteros-Arias, 2015; Tamori and Deng, 2011). Cell competition enables epithelia to actively eliminate emergent oncogenic cells as an endogenous tumor-suppression mechanism.…”

p53 pathway is involved in cell competition during mouse embryogenesis

“…Only a few studies reported cell competition phenomenon in mammals (28). Cells with a mutation in the Rpl24 gene (Rpl24 Bst/+ ), which encodes a component of ribosome protein in mouse, were outcompeted in chimeric embryos that were generated by injecting Rpl24…”

Mechanisms of cell competition emerging from Drosophila studies

“…Mutations in azot , a putative calcium binding protein gene induced by Myc cell competition, are reported to shorten lifespan and accumulate developmental defects, illustrating the possibility that cell competition optimizes progenitor cell pools during development and aging by eliminating defective cells [21*]. Cell competition phenomena in mammals seem to fit this paradigm [9]. It is suggested in the DNA damage field that ribosomal protein genes, being predominantly single copy and distributed throughout the genome in Drosophila as in mammals, might be ‘counted’ as sentinels of aneuploidy and other major genome alterations, and that Minute cells are eliminated due to their resemblance to aneuploid cells [48,49].…”

“…In Drosophila , cell competition has only been observed in vivo in proliferating epithelial tissues, such as the undifferentiated imaginal discs that comprise the precursor cells for adult structures, in the ovarian follicle, and in the adult gut [1,7,8*]. Several examples of cell competition have now also been described in mammalian systems [9]. …”

“…There is particular interest in possible cell competition in cancer, because tumors generally differ genetically from surrounding cells and because many cell competition genes have mammalian homologs that are proto-oncogenes or tumor suppressors (Table 1). Cell competition has been comprehensively reviewed previously [10–13,9,14] and the present review serves to summarize recent developments in Drosophila , where there has been progress in understanding both apoptotic cell competition mechanisms and in mechanisms that involve cell extrusion from epithelia.…”