Nuclear stiffness through lamin A/C overexpression differentially modulates chromosomal instability biomarkers

Year: 2025

Type: article

Abstract: BACKGROUND INFORMATION: Mitosis is crucial for the faithful transmission of genetic material, and disruptions can result in chromosomal instability (CIN), a hallmark of cancer. CIN is a known driver of tumor heterogeneity and anti-cancer drug resistance, thus highlighting the need to assess CIN levels in cancer cells to design effective targeted therapy. While micronuclei are widely recognized as CIN markers, we have recently identified the toroidal nucleus, a novel ring-shaped nuclear phenotype arising as well from chromosome mis-segregation. RESULTS: Here, we examined whether increasing nuclear envelope stiffness through lamin A/C overexpression could affect the formation of toroidal nuclei and micronuclei. Interestingly, lamin A/C overexpression led to an increase in toroidal nuclei while reducing micronuclei prevalence. We demonstrated that chromatin compaction and nuclear stiffness drive the formation of toroidal nuclei. Furthermore, inhibition of autophagy and lysosomal function elevated the frequency of toroidal nuclei without affecting the number of micronuclei in the whole cell population. We demonstrated that this divergence between the two CIN biomarkers is independent of defects in lamin A processing. CONCLUSIONS AND SIGNIFICANCE: These findings uncover a complex interplay between nuclear architecture and levels of CIN, advancing our understanding of the mechanisms supporting genomic stability and further contributing to cancer biology.

Source: Biology of the Cell

DOI: 10.1111/boc.12001

Authors: Mireia Bosch‐Calvet, Alejandro Pérez‐Venteo, Alex Cebria‐Xart, Marta Garcia‐Cajide, Caroline Mauvezin

Institutions: Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Institute for Research in Biomedicine, Institut de Recerca Sant Joan de Déu

Language: English

Topic: Nuclear Structure and Function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,730

Funders: Ministerio de Ciencia, Innovación y Universidades, Ministerio de Ciencia e Innovación, Universitat de Barcelona, Agència de Gestió d'Ajuts Universitaris i de Recerca, Agencia Estatal de Investigación

OpenAlex ID: W4408026132