Vimentin and compressive forces shape genome integrity and cell survival

Glioblastoma, the most common and aggressive primary brain tumor, has a particularly poor prognosis, largely due to its pronounced yet poorly understood intratumoral heterogeneity. Single-cell transcriptomic analyses reveal that vimentin expression exhibits significant heterogeneity both within and across glioblastoma tumors.

Traditionally associated with enhanced cellular invasion, vimentin is shown here to play a critical role in maintaining nuclear shape and chromatin organization in glioblastoma cells, shielding them from compressive forces. Loss of vimentin results in nuclear deformation, chromatin remodeling and profound changes in gene expression. Remarkably, we demonstrate that external compressive forces, similar to vimentin deficiency, disrupt DNA damage response pathways.