LINC complex roles in epithelial cell architecture and 3D migration

LINC complex roles in epithelial cell architecture and 3D migration

Speaker: Dr Akis Karakesisoglou, Department of Biosciences, University of Durham

Host:  Franca Fraternali

Abstract: Cell migration requires interplay and synergy of multiple cellular compartments. Initially, extracellular cues instruct plasma membrane receptors to transmit forces via the cytoskeleton to the nuclear interior through the linker of the nucleoskeleton and cytoskeleton (LINC) complex. LINC re-structures and re-positions organelles, including the nucleus, allowing directed cell motility. Despite LINC being modulated in metastatic cancers, its roles in epithelial invasiveness are unknown. We show that LINC disruption compromises organelle positioning and reduces motility in non-restrictive 2D and 3D growth environments. However, in confined 3D milieus, LINC disruption enhances collective cell migration, which we attribute to the decreased nuclear stiffness and pronounced cell-cell adhesions of the LINC mutants. Our findings suggest that reconfigured nucleo-cytoskeletal coupling mechanisms operate upon LINC complex disruption, which increases nuclear malleability. Together, these results suggest that LINC deregulation in cancers may facilitate metastasis, as greater nuclear plasticity and enhanced multi-cellular migration facilitate infiltration into space-restrictive microenvironments, thus increasing the likelihood for secondary tumour formation.