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ATF6 alpha regulates morphological changes associated with senescence in human fibroblasts
- Source :
- Oncotarget, Oncotarget, Impact journals, 2016, 7 (42), pp.67699--67715. ⟨10.18632/oncotarget.11505⟩, Oncotarget, 2016, 7 (42), pp.67699--67715. ⟨10.18632/oncotarget.11505⟩
- Publication Year :
- 2016
- Publisher :
- HAL CCSD, 2016.
-
Abstract
- // Clementine Druelle 1,6,* , Claire Drullion 1,* , Julie Desle 1,* , Nathalie Martin 1 , Laure Saas 1 , Johanna Cormenier 1 , Nicolas Malaquin 1,7 , Ludovic Huot 2 , Christian Slomianny 3 , Fatima Bouali 1 , Chantal Vercamer 1 , David Hot 2 , Albin Pourtier 1 , Eric Chevet 4,5 , Corinne Abbadie 1 and Olivier Pluquet 1 1 Universite de Lille, Institut Pasteur de Lille, CNRS UMR8161, Mechanisms of Tumourigenesis and Targeted Therapies, Lille, France 2 Universite de Lille, Institut Pasteur de Lille, INSERM, CNRS UMR8204, Centre d’Infection et d’Immunite de Lille, Lille, France 3 Universite de Lille, INSERM U1003, Villeneuve d’Ascq, France 4 Oncogenesis, Stress, Signaling, INSERM ER-440 Universite de Rennes, Rennes, France 5 Centre de Lutte Contre le Cancer Eugene Marquis, Rennes, France 6 Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland 7 Institut du Cancer de Montreal, Montreal, QC, Canada * These authors have contributed equally to this work Correspondence to: Olivier Pluquet, email: // Keywords : senescence, unfolded protein response, ATF6α, endoplasmic reticulum, normal human dermal fibroblast, Gerotarget Received : June 22, 2016 Accepted : August 02, 2016 Published : August 22, 2016 Abstract 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.
- Subjects :
- 0301 basic medicine
Senescence
Adult
Male
endoplasmic-reticulum stress
senescence
Cellular senescence
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
er stress
medicine.disease_cause
Endoplasmic Reticulum
Dermal fibroblast
03 medical and health sciences
Research Paper: Gerotarget (Focus on Aging)
Microscopy, Electron, Transmission
medicine
Humans
cellular senescence
Cell shape
normal human dermal fibroblast
Child
membrane
Cells, Cultured
disease
Gerotarget
pathway
Gene Expression Profiling
Infant
cytoskeleton
Dermis
unfolded protein response
Fibroblasts
ATF6α
Endoplasmic Reticulum Stress
gene-expression
3. Good health
Cell biology
Activating Transcription Factor 6
030104 developmental biology
Oncology
Unfolded protein response
cells
Female
RNA Interference
Carcinogenesis
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Database :
- OpenAIRE
- Journal :
- Oncotarget, Oncotarget, Impact journals, 2016, 7 (42), pp.67699--67715. ⟨10.18632/oncotarget.11505⟩, Oncotarget, 2016, 7 (42), pp.67699--67715. ⟨10.18632/oncotarget.11505⟩
- Accession number :
- edsair.doi.dedup.....4cd65dbad1d6c9e3a07513cf11a46fb2