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ATF6α regulates morphological changes associated with senescence in human fibroblasts

Cellular senescence is known as an anti-tumor barrier and is characterized by a number of determinants including cell cycle arrest, senescence associated β-galactosidase activity and secretion of pro-inflammatory mediators. Senescent cells are also subjected to enlargement, cytoskeleton-mediated sha...

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Autores principales: Druelle, Clémentine, Drullion, Claire, Deslé, Julie, Martin, Nathalie, Saas, Laure, Cormenier, Johanna, Malaquin, Nicolas, Huot, Ludovic, Slomianny, Christian, Bouali, Fatima, Vercamer, Chantal, Hot, David, Pourtier, Albin, Chevet, Eric, Abbadie, Corinne, Pluquet, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356513/
https://www.ncbi.nlm.nih.gov/pubmed/27563820
http://dx.doi.org/10.18632/oncotarget.11505
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author Druelle, Clémentine
Drullion, Claire
Deslé, Julie
Martin, Nathalie
Saas, Laure
Cormenier, Johanna
Malaquin, Nicolas
Huot, Ludovic
Slomianny, Christian
Bouali, Fatima
Vercamer, Chantal
Hot, David
Pourtier, Albin
Chevet, Eric
Abbadie, Corinne
Pluquet, Olivier
author_facet Druelle, Clémentine
Drullion, Claire
Deslé, Julie
Martin, Nathalie
Saas, Laure
Cormenier, Johanna
Malaquin, Nicolas
Huot, Ludovic
Slomianny, Christian
Bouali, Fatima
Vercamer, Chantal
Hot, David
Pourtier, Albin
Chevet, Eric
Abbadie, Corinne
Pluquet, Olivier
author_sort Druelle, Clémentine
collection PubMed
description Cellular senescence is known as an anti-tumor barrier and is characterized by a number of determinants including cell cycle arrest, senescence associated β-galactosidase activity and secretion of pro-inflammatory mediators. Senescent cells are also subjected to enlargement, cytoskeleton-mediated shape changes and organelle alterations. However, the underlying molecular mechanisms responsible for these last changes remain still uncharacterized. Herein, we have identified the Unfolded Protein Response (UPR) as a player controlling some morphological aspects of the senescent phenotype. We show that senescent fibroblasts exhibit ER expansion and mild UPR activation, but conserve an ER stress adaptive capacity similar to that of exponentially growing cells. By genetically invalidating the three UPR sensors in senescent fibroblasts, we demonstrated that ATF6α signaling dictates senescence-associated cell shape modifications. We also show that ER expansion and increased secretion of the pro-inflammatory mediator IL6 were partly reversed by silencing ATF6α in senescent cells. Moreover, ATF6α drives the increase of senescence associated-β-galactosidase activity. Collectively, these findings unveil a novel and central role for ATF6α in the establishment of morphological features of senescence in normal human primary fibroblasts.
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spelling pubmed-53565132017-03-24 ATF6α regulates morphological changes associated with senescence in human fibroblasts Druelle, Clémentine Drullion, Claire Deslé, Julie Martin, Nathalie Saas, Laure Cormenier, Johanna Malaquin, Nicolas Huot, Ludovic Slomianny, Christian Bouali, Fatima Vercamer, Chantal Hot, David Pourtier, Albin Chevet, Eric Abbadie, Corinne Pluquet, Olivier Oncotarget Research Paper: Gerotarget (Focus on Aging) Cellular senescence is known as an anti-tumor barrier and is characterized by a number of determinants including cell cycle arrest, senescence associated β-galactosidase activity and secretion of pro-inflammatory mediators. Senescent cells are also subjected to enlargement, cytoskeleton-mediated shape changes and organelle alterations. However, the underlying molecular mechanisms responsible for these last changes remain still uncharacterized. Herein, we have identified the Unfolded Protein Response (UPR) as a player controlling some morphological aspects of the senescent phenotype. We show that senescent fibroblasts exhibit ER expansion and mild UPR activation, but conserve an ER stress adaptive capacity similar to that of exponentially growing cells. By genetically invalidating the three UPR sensors in senescent fibroblasts, we demonstrated that ATF6α signaling dictates senescence-associated cell shape modifications. We also show that ER expansion and increased secretion of the pro-inflammatory mediator IL6 were partly reversed by silencing ATF6α in senescent cells. Moreover, ATF6α drives the increase of senescence associated-β-galactosidase activity. Collectively, these findings unveil a novel and central role for ATF6α in the establishment of morphological features of senescence in normal human primary fibroblasts. Impact Journals LLC 2016-08-22 /pmc/articles/PMC5356513/ /pubmed/27563820 http://dx.doi.org/10.18632/oncotarget.11505 Text en Copyright: © 2016 Druelle et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Gerotarget (Focus on Aging)
Druelle, Clémentine
Drullion, Claire
Deslé, Julie
Martin, Nathalie
Saas, Laure
Cormenier, Johanna
Malaquin, Nicolas
Huot, Ludovic
Slomianny, Christian
Bouali, Fatima
Vercamer, Chantal
Hot, David
Pourtier, Albin
Chevet, Eric
Abbadie, Corinne
Pluquet, Olivier
ATF6α regulates morphological changes associated with senescence in human fibroblasts
title ATF6α regulates morphological changes associated with senescence in human fibroblasts
title_full ATF6α regulates morphological changes associated with senescence in human fibroblasts
title_fullStr ATF6α regulates morphological changes associated with senescence in human fibroblasts
title_full_unstemmed ATF6α regulates morphological changes associated with senescence in human fibroblasts
title_short ATF6α regulates morphological changes associated with senescence in human fibroblasts
title_sort atf6α regulates morphological changes associated with senescence in human fibroblasts
topic Research Paper: Gerotarget (Focus on Aging)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356513/
https://www.ncbi.nlm.nih.gov/pubmed/27563820
http://dx.doi.org/10.18632/oncotarget.11505
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