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

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 accelerate...

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Autores principales: Rapisarda, Valentina, Borghesan, Michela, Miguela, Veronica, Encheva, Vesela, Snijders, Ambrosius P., Lujambio, Amaia, O’Loghlen, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357738/
https://www.ncbi.nlm.nih.gov/pubmed/28273461
http://dx.doi.org/10.1016/j.celrep.2017.02.012
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author Rapisarda, Valentina
Borghesan, Michela
Miguela, Veronica
Encheva, Vesela
Snijders, Ambrosius P.
Lujambio, Amaia
O’Loghlen, Ana
author_facet Rapisarda, Valentina
Borghesan, Michela
Miguela, Veronica
Encheva, Vesela
Snijders, Ambrosius P.
Lujambio, Amaia
O’Loghlen, Ana
author_sort Rapisarda, Valentina
collection PubMed
description 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.
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spelling pubmed-53577382017-03-28 Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway Rapisarda, Valentina Borghesan, Michela Miguela, Veronica Encheva, Vesela Snijders, Ambrosius P. Lujambio, Amaia O’Loghlen, Ana Cell Rep Article 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. Cell Press 2017-03-07 /pmc/articles/PMC5357738/ /pubmed/28273461 http://dx.doi.org/10.1016/j.celrep.2017.02.012 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rapisarda, Valentina
Borghesan, Michela
Miguela, Veronica
Encheva, Vesela
Snijders, Ambrosius P.
Lujambio, Amaia
O’Loghlen, Ana
Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway
title Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway
title_full Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway
title_fullStr Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway
title_full_unstemmed Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway
title_short Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway
title_sort integrin beta 3 regulates cellular senescence by activating the tgf-β pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357738/
https://www.ncbi.nlm.nih.gov/pubmed/28273461
http://dx.doi.org/10.1016/j.celrep.2017.02.012
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