Cells induced into senescence exhibit a marked increase in the secretion of pro-inflammatory cytokines termed senescence-associated secretory phenotype (SASP). Here we report that SASP from senescent stromal fibroblasts promote spontaneous morphological changes accompanied by an aggressive migratory behavior in originally non-motile human breast cancer cells. This phenotypic switch is coordinated, in space and time, by a dramatic reorganization of the actin and microtubule filament networks, a discrete polarization of EB1 comets, and an unconventional front-to-back inversion of nucleus-MTOC polarity. SASP-induced morphological/migratory changes are critically dependent on microtubule integrity and dynamics, and are coordinated by the inhibition of RhoA and cell contractility. RhoA/ROCK inhibition reduces focal adhesions and traction forces, while promoting a novel gliding mode of migration.
Aifuwa, I., Giri, A., Longe, N., Lee, S. H., An, S. S., & Wirtz, D. (2015). Senescent stromal cells induce cancer cell migration via inhibition of RhoA/ROCK/myosin-based cell contractility. Oncotarget, 6(31), 30516–30531. https://doi.org/10.18632/oncotarget.5854