Nuclear Mechanics and Cancer Cell Migration.

As a cancer cell invades adjacent tissue, penetrates a basement membrane barrier, or squeezes into a blood capillary, its nucleus can be greatly constricted. Here, we examine: (1) the passive and active deformation of the nucleus during 3D migration; (2) the nuclear structures-namely, the lamina and chromatin-that govern nuclear deformability; (3) the effect of large nuclear deformation on DNA and nuclear factors; and (4) the downstream consequences of mechanically stressing the nucleus. We focus especially on recent studies showing that constricted migration causes nuclear envelope rupture and excess DNA damage, leading to cell cycle suppression, possibly cell death, and ultimately it seems to heritable genomic variation. We first review the latest understanding of nuclear dynamics during cell migration, and then explore the functional effects of nuclear deformation, especially in relation to genome integrity and potentially cancerous mutations.