Work

Extracellular matrix stiffness drives post-mitotic nuclear pore complex assembly to promote neuroblastoma pathogenesis

Year: 2026

Type: article

Abstract: Nuclear pore complex (NPC) undergoes dynamic changes in physiology and pathology, yet its roles in neuroblastoma (NB) remain unclear. We demonstrated that rigid extracellular matrix (ECM) facilitated NPC-mediated nucleocytoplasmic transport in NB cells using super-resolution microscopy, a deep learning algorithm, and photobleaching. NPC transport enhancer Pitstop-2 stimulated cell migration, while blocker WGA repressed it. Mechanistically, rigid ECM downregulated lamin A/C, leading to E2F4 upregulation, PLK1 reduction, mitosis prolongation, and ultimately enhanced post-mitotic NPC assembly. U2OS-CRISPR-Nup96-SNAP visualized the delayed mitotic progression and enhanced post-mitotic NPC assembly under lamin A/C knockdown. Clinical NB samples confirmed a positive correlation between NPC number and tissue stiffness. Furthermore, patient-derived organoids confirmed that both WGA and PLK1 inhibitor significantly suppressed tumor cell viability. Our study established that ECM stiffness drives NB cell migration through a lamin A/C/E2F4/PLK1 axis, governing post-mitotic NPC assembly and transport function. Targeting NPC-mediated transport may represent a promising therapeutic strategy for NB.

Source: Cell Reports

DOI: 10.1016/j.celrep.2025.116858