Metabolic regulation of cell competition

Abstract

Cell Competition is a selective process by which viable cells are eliminated from developing or adult tissues by interactions with their neighbors. In many cases, the eliminated cells (losers) display reduced fitness, yet they would be able to sustain tissue growth or maintenance in a homotypic environment, and are only eliminated when confronted with surrounding wild type cells (winners). In addition, cells with oncogenic mutations that do not show reduced fitness can also be eliminated from tissues when surrounded by wild type cells. Depending on the context, transformed cells can also become supercompetitors and eliminate surrounding wild type cells, thereby promoting tumor formation. Several factors have been shown to play essential roles in Cell Competition, including genes relevant in developmental growth, tumor formation and epithelial apico-basal polarity. Recent discoveries, however, suggest that energy metabolism plays a central role in very different models of cell competition. Here we review the involvement of mitochondrial dynamics and metabolism, autophagy and nutritional status in cell competition and discuss the possible implications of this emerging field.

Keywords: Apoptosis; Autophagy; Energy metabolism; Glycolysis; Lactate; Mitochondria; Tumor formation; Tumor suppression; Warburg effect.