How extracellular matrix stiffness promotes neuroblastoma pathogenesis
The mechanism of neuroblastoma (NB) pathogenesis and metastasis is not well understood,
The researchers in this study identify a mechanosensitive pathway linking extracellular matrix (ECM) stiffness to neuroblastoma cell migration.
The authors demonstrate that rigid ECM drives NB cell migration by enhancing post-mitotic nuclear pore complex (NPC) assembly and transport, They also show that NPC transport enhancer Pitstop-2 stimulated cell migration, while blocker WGA repressed it.
The researchers show that rigid ECM represses lamin A/C, prolongs mitosis via E2F4/PLK1, and promotes NPC assembly and inhibition of lamin A/C or PLK1 enhances, but NPC blockade impairs, cellular migration.
Furthermore, clinical data using patient-derived organoids confirmed that both WGA and PLK1 inhibitor significantly suppressed tumor cell viability suggesting targeting NPC function as a potential therapeutic strategy for neuroblastoma.
https://www.cell.com/cell-reports/fulltext/S2211-1247(25)01630-4
https://sciencemission.com/ECM-stiffness--to-promote-neuroblastoma
