Ras signalling at the actin cortex: Coordinating local and global changes to cell morphology

Ras proteins modulate key cellular signalling pathways and drive excessive proliferation when mutated in cancer. However, they also influence actin cytoskeleton organisation. In the model organism Dictyostelium, domains of active Ras pattern the plasma membrane and locally reorganise the actin cortex, driving the formation of actin-based protrusions. Recent work has identified analogous Ras-dependent actin structures in cancer cells, including actin waves, protrusions and membrane blebs, which promote cell survival and motility. In addition, Ras activation induces changes to signalling networks and gene expression that result in cell-wide changes to actin network architecture, cortex mechanics and cell shape. This review examines how the local and global effects of Ras signalling on the actin cytoskeleton are coordinated and how they contribute to cytoskeletal plasticity during cancer progression.