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, Denis Wirtz

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)30516-30531
Number of pages16
JournalOncotarget
Volume6
Issue number31
DOIs
StatePublished - Jan 1 2015

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Keywords

  • SASP
  • Senescence

ASJC Scopus subject areas

  • Oncology

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