Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/226590
Nuclear stiffness through lamin A/C overexpression differentially modulates chromosomal instability biomarkers
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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.
Matèries (anglès)
Citació
Citació
BOSCH CALVET, Mireia, PÉREZ VENTEO, Alejandro, CEBRIA XART, Alex, GARCIA CAJIDE, Marta, MAUVEZIN, Caroline. Nuclear stiffness through lamin A/C overexpression differentially modulates chromosomal instability biomarkers. _Biology of the Cell_. 2025. Vol. 117, núm. 2, pàgs. e12001. [consulta: 7 de febrer de 2026]. ISSN: 0248-4900. [Disponible a: https://hdl.handle.net/2445/226590]