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Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway.

Authors :
Rapisarda V
Borghesan M
Miguela V
Encheva V
Snijders AP
Lujambio A
O'Loghlen A
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.)

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