Priority Research Papers:
Senescent stromal cells induce cancer cell migration via inhibition of RhoA/ROCK/myosin-based cell contractility
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Ivie Aifuwa1,2, Anjil Giri1,2, Nick Longe2, Sang Hyuk Lee2, Steven S. An1,4 and Denis Wirtz1,2,3
1 Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland, USA
2 Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA
3 Departments of Pathology and Oncology, Sydney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA
4 Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Denis Wirtz, email:
Keywords: SASP, senescence
Received: August 06, 2015 Accepted: August 29, 2015 Published: October 01, 2015
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.
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