Journal
ONCOTARGET
Volume 6, Issue 31, Pages 30516-30531Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5854
Keywords
SASP; senescence
Categories
Funding
- NIH [U54CA143868, R01CA174388]
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Cells induced into senescence exhibit a marked increase in the secretion of proinflammatory 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.
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