Senescent stromal cells induce cancer cell migration via inhibition of RhoA/ROCK/myosin-based cell contractility
| Autor: | Sang Hyuk Lee, Ivie Aifuwa, Nick Longe, Anjil Giri, Steven S. An, Denis Wirtz |
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| Rok vydání: | 2015 |
| Předmět: |
Gerontology
RHOA Time Factors senescence SASP Microtubules 0302 clinical medicine Cell Movement Cell polarity Medicine Cellular Senescence 0303 health sciences rho-Associated Kinases biology Cell Polarity humanities 3. Good health Phenotype Oncology 030220 oncology & carcinogenesis MCF-7 Cells Female Cell aging Microtubule-Associated Proteins Signal Transduction Stromal cell Breast Neoplasms Myosins Transfection Focal adhesion 03 medical and health sciences Microtubule Paracrine Communication Humans Cell Shape Protein Kinase Inhibitors Actin 030304 developmental biology Focal Adhesions business.industry fungi Fibroblasts Actins Cancer cell Mutation biology.protein Cancer research business rhoA GTP-Binding Protein Priority Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Ivie Aifuwa 1,2 , Anjil Giri 1,2 , Nick Longe 2 , Sang Hyuk Lee 2 , Steven S. An 1,4 and Denis Wirtz 1,2,3 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. |
| Databáze: | OpenAIRE |
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