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Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway.
- Source :
-
Cell reports [Cell Rep] 2017 Mar 07; Vol. 18 (10), pp. 2480-2493. - Publication Year :
- 2017
-
Abstract
- Cellular senescence is an important in vivo mechanism that prevents the propagation of damaged cells. However, the precise mechanisms regulating senescence are not well characterized. Here, we find that ITGB3 (integrin beta 3 or β3) is regulated by the Polycomb protein CBX7. β3 expression accelerates the onset of senescence in human primary fibroblasts by activating the transforming growth factor β (TGF-β) pathway in a cell-autonomous and non-cell-autonomous manner. β3 levels are dynamically increased during oncogene-induced senescence (OIS) through CBX7 Polycomb regulation, and downregulation of β3 levels overrides OIS and therapy-induced senescence (TIS), independently of its ligand-binding activity. Moreover, cilengitide, an αvβ3 antagonist, has the ability to block the senescence-associated secretory phenotype (SASP) without affecting proliferation. Finally, we show an increase in β3 levels in a subset of tissues during aging. Altogether, our data show that integrin β3 subunit is a marker and regulator of senescence.<br /> (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Aged, 80 and over
Aging metabolism
Animals
Cell Line
Cells, Cultured
Child
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Extracellular Matrix metabolism
Fibroblasts metabolism
Humans
Integrin beta3 genetics
Isotope Labeling
Mice
Polycomb Repressive Complex 1 metabolism
Protein Subunits metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Tumor Suppressor Protein p53 metabolism
Up-Regulation genetics
Cellular Senescence genetics
Integrin beta3 metabolism
Signal Transduction
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 18
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 28273461
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.02.012