Fig. 6 | Nature Communications

Fig. 6

From: LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration

Fig. 6

Model of LINC complex-, Lis1-dependent nucleus-centrosome linkage control of MT1-MMP matrix digest-on-demand response. Confined migration of tumor cells through dense 3D collagen network results in nucleus confinement by constricting collagen fibrils. Nucleus-microtubule cytoskeleton linkage through LINC complex and dynein heavy load factor Lis1 and cortical anchoring of microtubules is required for centrosome and MT1-MMP endosome positioning and for targeted delivery of MT1-MMP to invadopodia. Nucleus movement is facilitated by localized invadopodia-based pericellular proteolysis of confining fibrils ahead of the nucleus. Open arrows represent nuclear pulling force and counteracting forces from the matrix. Inset, scheme of nucleus-cytoskeletal linkage through LINC complex components nesprin and SUN in association with lamins. Lis1, probably in complex with dynein associates to the NE depending on Nesprin-2 and is involved in nucleus-microtubule linkage

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