Primary fibroblasts use a high pressure, "nuclear piston" mode of migration to move through highly cross-linked 3D extracellular matrices. Petrie et al. reveal that tumor cells with high levels of matrix metalloproteinase activity generally migrate by forming lamellipodia but, when their protease activity is inhibited, they can switch to the nuclear piston mechanism to force their nuclei through small gaps in the extracellular matrix.
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