Oncotarget

Priority Research Papers:

Senescent stromal cells induce cancer cell migration via inhibition of RhoA/ROCK/myosin-based cell contractility

Ivie Aifuwa, Anjil Giri, Nick Longe, Sang Hyuk Lee, Steven S. An and Denis Wirtz _

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Oncotarget. 2015; 6:30516-30531. https://doi.org/10.18632/oncotarget.5854

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Abstract

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

Correspondence to:

Denis Wirtz, email:

Keywords: SASP, senescence

Received: August 06, 2015 Accepted: August 29, 2015 Published: October 01, 2015

Abstract

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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