Understanding the mechanobiology of cell competition during cancer initiation*

Cell competition is a vital process wherein healthy cells collectively identify and eliminate mutant cells within the body to maintain the overall well-being and function of tissues. It also underlies an inherent anti-cancer process, known as the epithelial defense against cancer (EDAC), which plays a crucial role in preventing the development of tumors. Despite its importance, the precise mechanisms governing EDAC have remained largely unknown. We are working to uncover how cellular forces and tissue mechanics influence EDAC. In our investigations, we initially observed that the stiffness of the extracellular matrix is a crucial factor in determining the effectiveness of EDAC. We found that when the matrix becomes stiffer, it impairs the body's ability to defend against the mutant cells. Additionally, we made the intriguing discovery that, before the removal of transformed cells, they experience compressive stress. Notably, this stress is not driven by differences in cell proliferation but rather by variations in mechanical properties, creating a competitive environment between normal and mutant cells. Furthermore, our research is delving into the role of nuclear mechanics in this intricate process. In summary, our findings are challenging the traditional paradigm of cancer research by emphasizing the significance of mechanobiology in understanding the initiation of cancer.