Invited Talk

The effect of Ras oncogenes on cell mechanics

University of Sheffield, School of Biosciences, B2-05 Florey Building Western Bank, S10 2TN, Sheffield, UK

Contact:  | Website

During mitosis cells undergo a series of shape and mechanical changes, driven by dynamic re-arrangement of the acto-myosin cytoskeleton. This enables them to round up and generate space for spindle assembly and chromosome segregation. We investigated how activation of Ras oncogenes alter mitotic cell shape, mechanics and adhesion in normal epithelial cells. We find that short-term Ras induction activates downstream MEK/ERK signalling to enhance cell rounding and stiffening at mitosis. In single cells, these Ras-dependent changes allow cells to round up and divide faithfully when confined underneath stiff hydrogels, a condition which introduces catastrophic errors in chromosome segregation in non-transformed cells. When Ras is activated in cells within an epithelial monolayer, the alterations to mitotic cell mechanics combined with changes in cell/cell adhesion result in mis-orientated, out-of-plane cell divisions and loss of monolayer integrity. These results reveal how oncogenic Ras directly alters the cell division process to promote both the initial breakdown of epithelial structure and the subsequent proliferation of individual cells in mechanically stiff tumour-like environments.