RT Journal Article
SR Electronic
T1 Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.17.468902
DO 10.1101/2021.11.17.468902
A1 Ivie Aifuwa
A1 Jude M. Philip
A1 Byoung Choul Kim
A1 Teresa R. Luperchio
A1 Angela Jimenez
A1 Tania Perestrelo
A1 Sang-Hyuk Lee
A1 Nick Longe
A1 Karen Reddy
A1 Taekjip Ha
A1 Denis Wirtz
YR 2021
UL http://biorxiv.org/content/early/2021/11/18/2021.11.17.468902.abstract
AB 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 a defective outside-in mechanotransduction, from actomyosin fibers in the cytoplasm to the nuclear lamina, thereby triggering a cascade of biophysical and biomolecular changes in cells that associate with malignant transformations.Competing Interest StatementThe authors have declared no competing interest.