Paclitaxel compromises nuclear integrity in interphase through SUN2-mediated cytoskeletal coupling.

ABSTRACT: Regulation of lamin A/C levels and distribution is crucial for nuclear integrity and mechanotransduction via the linker of nucleoskeleton and cytoskeleton (LINC) complex. Dysregulation of lamin A/C correlates with poor cancer prognosis, and its levels determine sensitivity to the microtubule-stabilising drug paclitaxel. Paclitaxel is well-known for disrupting mitosis, yet it also reduces tumour size in slow-dividing tumours, indicating an additional, poorly characterised interphase mechanism. Here, we reveal that paclitaxel induces nuclear aberrations in interphase through SUN2-dependent lamin A/C disruption. Using advanced optical imaging and electron cryo-tomography, we show the formation of aberrant microtubule-vimentin bundles during paclitaxel treatment, which coincides with nuclear d

SUBMITTER: Hale T 

PROVIDER: S-EPMC12863304 | biostudies-literature | 2026 Jun

REPOSITORIES: biostudies-literature