Title :

TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence

Author(s) :

Farfariello, Valerio [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Gordienko, Dmitri [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Mesilmany, Lina [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Touil, Yasmine [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Germain, Emmanuelle [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Fliniaux, Ingrid [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Desruelles, Emilie [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Gkika, Dimitra [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Roudbaraki, Morad [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Shapovalov, George [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Noyer, Lucile [Auteur]
New York University Langone Medical Center [NYU Langone Medical Center]
Lebas, Mathilde [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Allart, Laurent [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Zienthal-Gelus, Nathalie [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Iamshanova, Oksana [Auteur]
Bonardi, Franck [Auteur]
Figeac, Martin [Auteur]
Laine, William [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Kluza, Jerome [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Marchetti, Philippe [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Quesnel, Bruno [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Metzger, Daniel [Auteur]
Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC]
Bernard, David [Auteur]
Parys, Jan [Auteur]
Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven]
Lemonnier, Loïc [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]
Prevarskaya, Natalia [Auteur]
Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL]

Journal title :

Nature Communications

Pages :

956

Publisher :

Nature Publishing Group

Publication date :

2022-12

ISSN :

2041-1723

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Abstract Cellular senescence is implicated in a great number of diseases including cancer. Although alterations in mitochondrial metabolism were reported as senescence drivers, the underlying mechanisms remain elusive. We ...
Show more >Abstract Cellular senescence is implicated in a great number of diseases including cancer. Although alterations in mitochondrial metabolism were reported as senescence drivers, the underlying mechanisms remain elusive. We report the mechanism altering mitochondrial function and OXPHOS in stress-induced senescent fibroblasts. We demonstrate that TRPC3 protein, acting as a controller of mitochondrial Ca 2+ load via negative regulation of IP 3 receptor-mediated Ca 2+ release, is down regulated in senescence regardless of the type of senescence inducer. This remodelling promotes cytosolic/mitochondrial Ca 2+ oscillations and elevates mitochondrial Ca 2+ load, mitochondrial oxygen consumption rate and oxidative phosphorylation. Re-expression of TRPC3 in senescent cells diminishes mitochondrial Ca 2+ load and promotes escape from OIS-induced senescence. Cellular senescence evoked by TRPC3 downregulation in stromal cells displays a proinflammatory and tumour-promoting secretome that encourages cancer epithelial cell proliferation and tumour growth in vivo. Altogether, our results unravel the mechanism contributing to pro-tumour behaviour of senescent cells.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL