We recently proved that cell death of keratinocytes can be the driving force for skin tumorigenesis. However, little is known on how dying or dead
keratinocytes affect the cancer stem cell niche. Here we will map the contribution of different types of regulated cell death to skin tumorigenesis
and identify crucial mediators of keratinocyte death. Key molecules for cell death regulation will be manipulated to test whether altered cell death has therapeutic potential for cancer treatments.
By combining CRISPR-Cas9 screenings, mouse transgenesis and functional studies in mouse and human skin, this research will reveal how
keratinocyte death affects the cancer stem cell niche and what are its implications for tumour formation and growth. We expect that these findings can be extrapolated to other tissues and provide insight into how cell death pathways can be exploited not only to induce quiescence in tumorigenic contexts, but also to improve stem cell-based therapies.