Metastasis involves the spread of cancer cells to sites that are distant from the original tumour. Efficient dissemination often requires these cells to travel through extremely tight spaces, but the factors allowing this ability have remained elusive. Now, Michael Olson and colleagues (Rudzka et al., 2019) identify the signalling pathways that enable cells to move through constricted spaces by studying cells that can pass through microporous membranes in culture. Although these cells (pore-selected cells), and their nuclei, are smaller than the starting parent population, these properties are not sufficient for efficient migration through narrow diameter pores or dense collagen matrices. Instead, the authors show that anisotropic arrangements of actin filaments, total F-actin levels and focal adhesion densities are all reduced in pore-selected cells, which was associated with decreased cellular stiffness. By using transcriptional profiling, the authors find that expression of target genes of the mitogen-activated protein kinase (MAPK) pathway are altered in pore-selected cells. Inhibition of the MAPK activator MEK reverses the cytoskeletal changes observed in these cells, and increases cellular stiffness. Moreover, ectopic expression of activated MAPK regulators promotes reductions in F-actin levels and anisotropy, focal adhesion density and cellular stiffness. Together, these findings indicate that MAPK signalling directs the plasticity of cancer cells, which could facilitate their passage through constrained spaces.

• © 2019. Published by The Company of Biologists Ltd