Lamin B2 follows lamin A/C- mediated nuclear mechanics and cancer cell invasion efficacy

Interstitial tumor cell invasion depends upon complex mechanochemical adaptation of both cell body and the rigid nucleus in response to extracellular tissue topologies. Nuclear mechanics during cell migration through confined environments is controlled by A-type lamins, however, the contribution of B-type lamins to the deformability of the nucleus remains unclear. Using systematic expression regulation of different lamin isoforms, we applied multi-parameter wet-lab and in silico analysis to test their impact on nuclear mechanics, shape regulation, and cancer cell migration. Modulation of lamin A/C and B2 but not B1 isoforms controlled nuclear deformation and viscoelasticity, whereby lamin B2 generally followed lamin A/C-mediated effects. Cell migration rates were altered by 5 to 9-fold in dense collagen environments and synthetic devices, with accelerated rates after lamin downregulation and reverse effects after lamin upregulation, with migration rates strongly depending on nuclear shape change. These findings implicate cooperation of lamin B2 with lamin A/C in regulating nuclear mechanics for shape adaptation and migration efficacy. SummaryNuclear deformability during cancer cell invasion and metastasis is critically regulated by lamin A. Here, researchers showed that lamin B2 also contributes to nuclear mechanics, implicating cooperating lamin networks regulating nuclear integrity, migration efficacy, and metastatic tumor progression.