Abstract
Nuclear deformability plays a critical role in cell migration. During this process, the remodeling of internal components of the nucleus has a direct impact on DNA damage and cell behavior; however, how persistent migration promotes nuclear changes leading to phenotypical and functional consequences remains poorly understood. Here, we described that the persistent migration through physical barriers was sufficient to promote permanent modifications in migratory-altered cells. We found that lamin B1 altered its localization, concomitant with morphological and transcriptional changes. Migratory-altered cells showed alterations in cellular functions such as DNA repair and cell migration. We applied biochemical and biophysical approaches to identify that confined conditions altered the biomechanical response of the nucleus. Mechanistically, we determined that actin dynamics controlled the redistribution of lamin, and the basal levels of DNA damage in migratory-altered cells. Our observations reveal a novel role for confined cell conditions in consistent nuclear and genomic alterations that might handle the genetic instability and cellular heterogeneity in aging diseases and cancer.
Highlights
Persistent confined migration promotes permanent mophological changes.
Lamin B1 is redistribution in the nucleus of migratory altered cells.
Migratory-altered cells exhibit transcriptional and functional changes related to cell migration and survival.
Actin polymerization controls nuclear changes induced by cell migration.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Supplemental Information and movies