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Determining the molecular pathways that regulate mammalian cell competition

Joel Pearson

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Canadian Institutes of Health Research (CIHR)
Cancer begins in the body as a single mutated cell surrounded by normal (non-mutated) cells, and for the disease to develop the mutant cell must survive, multiply and eventually form a tumour. Interestingly, recent research has demonstrated that mutant cells and the normal cells surrounding them affect each another, and that this interaction can determine whether the mutant cell survives and continues to grow. One way that these normal and mutant cells interact is through a process called cell competition. The outcome of this process is that "fitter" cells (which can be either the mutant or the normal cells) survive while the less fit cells are killed. Cell competition can therefore be beneficial as a means by which normal cells eliminate mutated cells before they cause cancer; however, it can also be a process that is hijacked by mutant cells allowing them to survive and cause disease. Thus, targeting competition may represent an ideal means to treat cancer; either weakening mutant cells or strengthening normal cells may prevent expansion of mutated, cancerous cells. Unfortunately, little is known about how competition between mammalian cells is regulated, and the molecular mediators of this process are poorly understood. Our research will expose how cell competition is regulated in humans and how this process might impact cancer by identifying proteins that play important roles in regulating cell competition. This work will dramatically improve our understanding of how mutant cells interact with surrounding normal cells, and will expose molecular targets that can be used to diagnose, prevent, and/or treat cancer at very early stages.

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