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

  • Cell Rep. 2026 Feb 24;45(2):116858. doi: 10.1016/j.celrep.2025.116858.
Guo-Zhu Sun  1 ,  Chen Miao  1 ,  Wen-Hao Tian  1 ,  Jia-Long Cui  2 ,  Zhong-Qian Liu  2 ,  Yue Lou  2 ,  Qing-Ping Yao  2 ,  Kai Huang  2 ,  Fan Lv  3 ,  Ying-Xin Qi  4
Affiliations
  • 1. Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
  • 2. Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  • 3. Department of Pediatric General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
  • 4. Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China; Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China. Electronic address: [email protected].
PMID: 41575851 DOI: 10.1016/j.celrep.2025.116858
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.

Keywords
CP: cancer; CP: cell biology; PLK1; extracellular matrix stiffness; lamin A/C; mitosis; neuroblastoma; nuclear pore complex.
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