Cell competition, apoptosis and tumour development

Abstract

The phenomenon of cell competition is an interactive process originally discovered in the imaginal discs of Drosophila; it is a developmental mechanism that identifies and eliminates cells that are weaker than their neighbours or have features that make them different or not well adapted to their surroundings. It appears to be an important homeostatic mechanism to contribute to the general fitness of developing tissues. Here we discuss some of the basic features of cell competition and then focus on results indicating that cell competition is responsible for the removal of malignant or aberrant cells that may appear during development, although in certain circumstances it can revert its role to promote tumour growth. We also consider several recent studies that indicate that cell competition also occurs in vertebrates where it performs similar functions.

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.…”

Synergism between canoe and scribble mutations causes tumor-like overgrowth via Ras activation in neural stem cells and epithelia

“…It is important to remark, though, that these studies were not done by clonal NB analysis but in the homozygous mutant condition, and individual NB lineages were not analyzed in detail (NBII lineages had not even been described at that time). Contrary to what happens in homozygous mutant brains, NB mutant clones are surrounded by WT cells, which may counteract or even eliminate the clonal mutant cells, a phenomenon known as cell competition (Morata and Ballesteros-Arias, 2015). In the context of cancer biology, where tumors start with mutation(s) in one or a small group of cells, clonal analysis for studying the tumorigenic potential of particular gene mutations rather than analysis of the whole mutant tissue is a more disease-relevant scenario.…”

Slit-Robo Repulsive Signaling Extrudes Tumorigenic Cells from Epithelia

“…Cell-cell interactions suppress tumorigenesis by eliminating weak or aberrant cells from tissues in a conserved process called cell competition (reviewed in Tamori and Deng, 2011; de Beco et al, 2012; Levayer and Moreno, 2013; Amoyel and Bach, 2014; Morata and Ballesteros-Arias, 2015). One example of tumor-suppressive cell competition is the active removal of cells lacking scribble ( scrib ) or discs large ( dlg ), evolutionarily conserved apicobasal polarity genes (Brumby and Richardson, 2003; Igaki et al, 2009).…”