Title :

ATF6 alpha regulates morphological changes associated with senescence in human fibroblasts

Author(s) :

Druelle, Clementine [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Drullion, Claire [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Desle, Julie [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Martini, Nathalie [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Saas, Laure [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Cormenier, Johanna [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Malaquin, Nicolas [Auteur]
Huot, Ludovic [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Slomianny, Christian [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Bouali, Fatima [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Vercamer, Chantal [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Hot, David [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Plateforme d'expertises génomiques appliquées aux sciences expérimentales [Lille] [PEGASE-Biosciences]
Pourtier, Albin [Auteur]
Institut de biologie de Lille - IBL [IBLI]
Chevet, Eric [Auteur]
Oncogenesis Stress Signaling [OSS]
CRLCC Eugène Marquis [CRLCC]
Abbadie, Corinne [Auteur]
Université de Lille, Droit et Santé
Institut de biologie de Lille - IBL [IBLI]
Pluquet, Olivier [Auteur]
Institut de biologie de Lille - IBL [IBLI]

Journal title :

Oncotarget

Pages :

67699--67715

Publisher :

Impact journals

Publication date :

2016-08-22

ISSN :

1949-2553

English keyword(s) :

Unfolded protein response
Endoplasmic-reticulum stress
Er stress
Cellular senescence
Gene-expression
Cells
Cytoskeleton
Pathway
Membrane
Disease

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer

English abstract : [en]

Cellular senescence is known as an anti-tumor barrier and is characterized by a number of determinants including cell cycle arrest, senescence associated beta-galactosidase activity and secretion of pro-inflammatory ...
Show more >Cellular senescence is known as an anti-tumor barrier and is characterized by a number of determinants including cell cycle arrest, senescence associated beta-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 ATF6 alpha 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 ATF6a in senescent cells. Moreover, ATF6a drives the increase of senescence associated-beta-galactosidase activity. Collectively, these findings unveil a novel and central role for ATF6a in the establishment of morphological features of senescence in normal human primary fibroblasts.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL