Cell proliferation lies at the heart of the threat posed by tumours. It involves cellular growth, division and migration. The tissue surrounding a tumor physically limits its proliferation, which implies that cells that are able to produce effective tumour growth, as well as cells that migrate out of the original tumour, have been able to circumvent this physical limitation. Other factors in tissues, however, can contribute to stop cell proliferation, making it difficult to precisely evaluate the contribution of physical confinement. In this project I propose to specifically address the effect of physical confinement on normal and cancer cells that are dividing and migrating, using new pathophysiologically relevant in vitro approaches. More specifically I propose two main objectives, related to the pathogenic potential of tumour cells:1) Discover specific mechanisms that allow dividing cells to push surrounding tissue (a process known as mitotic cell rounding) and demonstrate that alterations in this process can lead to spindle assembly defects and eventually to mitotic cell death. This will open a new set of targets to specifically kill dividing tumour cells.2) Discover specific mechanisms that allow migrating cells to squeeze their nucleus through narrow gaps. The nucleus has been shown to be the main physical barrier to cell migration in tissues, and two types of cells are able to migrate through narrow gaps: immune cells and metastatic cells. By comparing these two types of cells, we hope to uncover mechanisms specific to metastatic cells, thus providing targets for anti-metastatic treatments that would not harm immune cells function.Understanding how cancer cells can achieve efficient proliferation and migration under external constraints will aid the design of new anti-cancer strategies. These strategies would be based on targeting these specific processes identified to be essential for cancer cells to circumvent physical constraints they encounter in vivo.