Mammalian Cell Competitions, Cell-in-Cell Phenomena and Their Biomedical Implications

Cell competition was first identified four decades ago as a mechanism to eliminate less fit cells during development in Drosophila melanogaster, and later postulated to be involved in tumorigenesis of human beings. However, evidence for a similar mechanism functional in mammals and tumors was missed until recent years. Like cell competition in fly, multiple forms of competition mechanisms were reported in mammalian system, and some of them were found participating in tumor initiation. Lately, entosis, a mechanism of cell cannibalisms responsible for the formation of cell-in-cell structures in human tumors, was identified as a novel member of ever-expanding family of mammalian cell competitions (MaCCs), and proposed to be able to promote clonal selection and tumor evolution. Thus, engulfment by neighboring cells other than the professional phagocytes, an issue still in debate in fly, was clearly demonstrated in mammals to be responsible for loser elimination. Competition mediated by cell-in-cell structures, formed by multiple cannibal mechanisms, constitutes a novel class of MaCCs. This review will summarize current research on mammalian cell competitions, followed by feature and mechanism analysis and their potential implications in the pathology and treatment of human tumors.