Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension.

ABSTRACT: The presence of senescent cells within tissues has been functionally linked to malignant transformations. Here, using tension-gauge tethers technology, particle-tracking microrheology, and quantitative microscopy, we demonstrate that senescent-associated secretory phenotype (SASP) derived from senescent fibroblasts impose nuclear lobulations and volume shrinkage on malignant cells, which stems from the loss of RhoA/ROCK/myosin II-based cortical tension. This loss in cytoskeletal tension induces decreased cellular contractility, adhesion, and increased mechanical compliance. These SASP-induced morphological changes are, in part, mediated by Lamin A/C. These findings suggest that SASP induces defective outside-in mechanotransduction from actomyosin fibers in the cytoplasm to the nuclear lami

SUBMITTER: Aifuwa I 

PROVIDER: S-EPMC9830950 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature