Grant: Project Grant

Age is still considered as the greatest cancer risk factor, but according to recent evidence, it could actually be the total number of divisions stem cells execute over a lifetime that really is the greatest risk factor. Indeed, combined with a natural selection favouring enhanced growth and survival abilities, the stochastic accumulation of genetic and epigenetic errors, which mainly occur during cell division, inevitably tends to transform our stem cells into cancer cells as they divide over the course of our lives. Most of our differentiated cells, in contrast, have limited division potentials, such that the risk that they progressively transform to initiate tumorigenesis is much smaller. Thus, this emerging theory essentially claims that the longer we live, the more our stem cells divide, the more they accumulate changes and can progress towards unscheduled growth and eventually, tumorigenesis. The eventual transformation of a stem cell into a cancer cell requires escaping from the in vivo mechanisms that keep stem cell proliferation under control. Indeed, when stem cells are taken outside of animals and cultured in vitro (in the absence of these in vivo control mechanisms), they readily proliferate to form a tumour. To understand the initial transformation steps that may underlie stem cell-based tumorigenesis, we therefore need to define those in vivo mechanisms that limit stem cell proliferation. One such mechanism ensures stem cells only divide when the tissue they serve needs new differentiated cells. Homeostatic stem cell regulation is conserved and its localized properties may offer potential means to influence individual stem cell population activities by drugs in vivo, which could greatly impact our medical strategies in regenerative medicine, and cancer prevention/treatment. We recently established a powerful model system in C. elegans in which we plan to efficiently elucidate how homeostatic stem cell regulation is locally achieved in vivo.