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Journal articles
TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence
Valerio Farfariello
1
Dmitri Gordienko
1
Lina Mesilmany
1
Yasmine Touil
2
Emmanuelle Germain
1
Ingrid Fliniaux
1
Emilie Desruelles
1
Dimitra Gkika
1
Morad Roudbaraki
1
George Shapovalov
1
Lucile Noyer
3
Mathilde Lebas
1
Laurent Allart
1
Nathalie Zienthal-Gelus
1
Oksana Iamshanova
4
Franck Bonardi
5
Martin Figeac
5
William Laine
2
Jerome Kluza
2
Philippe Marchetti
2
Bruno Quesnel
2
Daniel Metzger
6
David Bernard
7
Jan Parys
8
Loïc Lemonnier
1
Natalia Prevarskaya
1
Valerio Farfariello 1
Author ORCID : https://orcid.org/0000-0003-3918-0793
Dmitri Gordienko 1
Author
Lina Mesilmany 1
Author ORCID : https://orcid.org/0000-0003-2930-115X
Yasmine Touil 2
Author ORCID : https://orcid.org/0000-0002-2286-960X
Emmanuelle Germain 1
Author
Ingrid Fliniaux 1
Author
Emilie Desruelles 1
Author
Dimitra Gkika 1
Author
Morad Roudbaraki 1
Author
George Shapovalov 1
Author
Lucile Noyer 3
Author ORCID : https://orcid.org/0000-0002-1369-684X
Mathilde Lebas 1
Author
Laurent Allart 1
Author
Nathalie Zienthal-Gelus 1
Author
Oksana Iamshanova 4
Author
Franck Bonardi 5
Author
Bruno Quesnel 2
Author ORCID : https://orcid.org/0000-0002-6563-2709
Daniel Metzger 6
Author IdHAL : daniel-metzger ORCID : https://orcid.org/0000-0002-5555-046X
David Bernard 7
Author IdHAL : david-bernard ORCID : https://orcid.org/0000-0002-1557-2074
Jan Parys 8
Author ORCID : https://orcid.org/0000-0002-3591-4967
Loïc Lemonnier 1
Author ORCID : https://orcid.org/0000-0001-6200-5382
Natalia Prevarskaya 1
Author ORCID : https://orcid.org/0000-0003-0316-197X
1
PHYCELL - Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (Cité scientifique - Bâtiment SN3 - 59650 Villeneuve d’Ascq, France - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1003 (101, rue de Tolbiac, 75013 Paris - France)
- Université de Lille : U1003 (Lille - France)
2
CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers -
Université de Lille - Bâtiment Cancer - Place de Verdun -
59000 LILLE - France)
- Institut Pasteur de Lille (1 Rue du Professeur Calmette - Lille Cedex - 59019 - France)
- RIIP - Réseau International des Instituts Pasteur (25, rue du Dr Roux 75724 Paris Cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1277 (101, rue de Tolbiac, 75013 Paris - France)
- Université de Lille : UMR9020 (Lille - France)
- CHRU Lille - Centre Hospitalier Régional Universitaire [Lille] : UMR9020 (2, avenue Oscar Lambret - 59037 Lille Cedex - France)
- CNRS - Centre National de la Recherche Scientifique : UMR9020 (France)
3
NYU Langone Medical Center - New York University Langone Medical Center (333 E 38th St, New York, NY 10016 - United States)
- NYU - NYU System (United States)
4
Institute of Biochemistry and Molecular Medicine, University of Bern (Bühlstrasse 28, 3012 Bern - Switzerland)
5
Institut de Pathologie, Centre de Biologie Pathologie Génétique, CS 70001, CHRU de Lille, (France)
- CHRU Lille - Centre Hospitalier Régional Universitaire [Lille] (2, avenue Oscar Lambret - 59037 Lille Cedex - France)
6
IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire (Parc D'Innovation 1 Rue Laurent Fries - BP 10142 67404 Illkirch Cedex - France)
- UNISTRA - Université de Strasbourg : UMR7104 (4 rue Blaise Pascal - CS 90032 - 67081 Strasbourg cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1258 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7104 (France)
7
UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon (28, rue Laennec - 69373 Lyon - France)
- Centre Léon Bérard [Lyon] (28, rue Laennec 69373 LYON Cedex 08 - France)
- UCBL - Université Claude Bernard Lyon 1 (43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex - France)
- Université de Lyon (92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1052 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR5286 (France)
Abstract : 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.
Document type :
Journal articles
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https://hal-univ-lyon1.archives-ouvertes.fr/hal-03666578
Contributor : Brigitte Manship Connect in order to contact the contributor
Submitted on : Thursday, May 12, 2022 - 3:38:56 PM
Last modification on : Friday, May 13, 2022 - 2:43:57 PM
Contributor : Brigitte Manship Connect in order to contact the contributor
Submitted on : Thursday, May 12, 2022 - 3:38:56 PM
Last modification on : Friday, May 13, 2022 - 2:43:57 PM
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Identifiers
- HAL Id : hal-03666578, version 1
- DOI : 10.1038/s41467-022-28597-x
- PUBMEDCENTRAL : PMC8854551
Collections
UNIV-LYON1 | IGBMC | RIIP | UNIV-LILLE | CRCL | UDL | SITE-ALSACE | CANTHER | CNRS | INSERM
Citation
Valerio Farfariello, Dmitri Gordienko, Lina Mesilmany, Yasmine Touil, Emmanuelle Germain, et al.. TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence. Nature Communications, Nature Publishing Group, 2022, 13 (1), pp.956. ⟨10.1038/s41467-022-28597-x⟩. ⟨hal-03666578⟩
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