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Journal articles
Synthetic alkyl-ether-lipid promotes TRPV2 channel trafficking trough PI3K/Akt-girdin axis in cancer cells and increases mammary tumour volume
Maxime Guéguinou
1, 2
Romain Felix
1
Séverine Marionneau-Lambot
3
Thibauld Oullier
4
Aubin Penna
5
Sana Kouba
1
Audrey Gambade
1
Yann Fourbon
1
David Ternant
2
Christophe Arnoult
2
Gaëlle Simon
6, 7
Ana Maria Bouchet
1
Aurélie Chantôme
1
Thomas Harnois
5
Jean-Pierre Haelters
6, 7
Paul-Alain Jaffres
7
Gunther Weber
1
Philippe Bougnoux
1
François Carreaux
8
Olivier Mignen
9
Christophe Vandier
1
Marie Potier-Cartereau
1, *
*
Corresponding author
Maxime Guéguinou 1, 2
Author
Romain Felix 1
Author
Séverine Marionneau-Lambot 3
Author
Thibauld Oullier 4
Author
Aubin Penna 5
Author IdHAL : aubin-penna ORCID : https://orcid.org/0000-0002-1070-5990
Sana Kouba 1
Author
Audrey Gambade 1
Author
Yann Fourbon 1
Author
David Ternant 2
Author
Christophe Arnoult 2
Author
Gaëlle Simon 6, 7
Author Employer institution : Université de Brest
Ana Maria Bouchet 1
Author
Aurélie Chantôme 1
Author
Thomas Harnois 5
Author
Jean-Pierre Haelters 6, 7
Author
Paul-Alain Jaffres 7
Author IdHAL : paul-alain-jaffres ORCID : https://orcid.org/0000-0002-6692-6039
Gunther Weber 1
Author
Philippe Bougnoux 1
Author
François Carreaux 8
Author
Olivier Mignen 9
Author
Christophe Vandier 1
Author
Marie Potier-Cartereau 1
Correspondent author
1
N2C - Nutrition, croissance et cancer (U 1069) (Faculté de médecine, 10 Bd Tonnelle 37032 Tours Cedex 1 - France)
- Université de Tours (60 rue du Plat d'Étain, 37020 Tours cedex 1 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1069 (101, rue de Tolbiac, 75013 Paris - France)
2
GICC EA 7501 - Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (UFR de Médecine, Bâtiment Bretonneau, 10 boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01 - France)
- Université de Tours (60 rue du Plat d'Étain, 37020 Tours cedex 1 - France)
3
IRS-UN - Institut de Recherche en Santé de l'Université de Nantes (8 Quai Moncousu 44007 Nantes - France)
4
TENS - The Enteric Nervous System in gut and brain disorders [U1235] (Faculté de Médecine,
1 rue Gaston Veil,
44035 Nantes - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : 1235 (101, rue de Tolbiac, 75013 Paris - France)
- UFR MEDECINE - Université de Nantes - UFR de Médecine et des Techniques Médicales (1 rue Gaston Veil BP 53508 44035 NANTES Cedex 1 - France)
- UN - Université de Nantes (1, quai de Tourville - BP 13522 - 44035 Nantes cedex 1 - France)
5
STIM - Signalisation et Transports Ioniques Membranaires (Bât. B36 - Pôle Biologie Santé 1, rue Georges Bonnet TSA 51106
86073 Poitiers Cedex 9 - France)
- Université de Poitiers : EA7349 (15, rue de l'Hôtel Dieu - 86034 Poitiers Cedex - France)
- Université de Tours : EA7349 (60 rue du Plat d'Étain, 37020 Tours cedex 1 - France)
- CNRS - Centre National de la Recherche Scientifique : ERL7003 (France)
6
UBO - Université de Brest (Université de Bretagne Occidentale - 3 Rue des Archives 29238, Brest - France)
7
CEMCA - Chimie, Electrochimie Moléculaires et Chimie Analytique (6 Av Victor Le Gorgeu - BP 809 29285 BREST CEDEX - France)
- IBSAM - Institut Brestois Santé Agro Matière (Université de Brest- UBO
29238 Brest - France)
- UBO - Université de Brest (Université de Bretagne Occidentale - 3 Rue des Archives 29238, Brest - France)
- CNRS - Centre National de la Recherche Scientifique : UMR6521 (France)
- INC - Institut de Chimie du CNRS (3 Rue Michel-Ange 75 016 Paris - France)
- UBO - Université de Brest (Université de Bretagne Occidentale - 3 Rue des Archives 29238, Brest - France)
8
ISCR - Institut des Sciences Chimiques de Rennes (Campus de Beaulieu - Bât. 10 Avenue du Général Leclerc 35042 Rennes Cedex - France)
- UR1 - Université de Rennes 1 (2 rue du Thabor - CS 46510 - 35065 Rennes cedex - France)
- UNIV-RENNES - Université de Rennes (France)
- INSA Rennes - Institut National des Sciences Appliquées - Rennes (20, avenue des Buttes de Coësmes - CS 70839 - 35708 Rennes cedex 7 - France)
- ENSCR - Ecole Nationale Supérieure de Chimie de Rennes (France)
- CNRS - Centre National de la Recherche Scientifique : UMR6226 (France)
9
Inserm UMR 1227 Immunothérapies et Pathologies Lymphocytaires B (CHU Morvan, Université de Bretagne Occidentale, Brest, F-29609, France - France)
- CHU - BREST - Hôpital Morvan - CHRU de Brest (2 Avenue Maréchal Foch, 29200 Brest - France)
Abstract : The Transient Receptor Potential Vanilloid type 2 (TRPV2) channel is highly selective for Ca2+ and can be activated by lipids, such as LysoPhosphatidylCholine (LPC). LPC analogues, such as the synthetic alkyl-ether-lipid edelfosine or the endogenous alkyl-ether-lipid Platelet Activating Factor (PAF), modulates ion channels in cancer cells. This opens the way to develop alkyl-ether-lipids for the modulation of TRPV2 in cancer. Here, we investigated the role of 2-Acetamido-2-Deoxy-l-O-Hexadecyl-rac-Glycero-3-PhosphatidylCholine (AD-HGPC), a new alkyl-ether-lipid (LPC analogue), on TRPV2 trafficking and its impact on Ca2+ -dependent cell migration. The effect of AD-HGPC on the TRPV2 channel and tumour process was further investigated using calcium imaging and an in vivo mouse model. Using molecular and pharmacological approaches, we dissected the mechanism implicated in alkyl-ether-lipids sensitive TRPV2 trafficking. We found that TRPV2 promotes constitutive Ca2+ entry, leading to migration of highly metastatic breast cancer cell lines through the PI3K/Akt-Girdin axis. AD-HGPC addresses the functional TRPV2 channel in the plasma membrane through Golgi stimulation and PI3K/Akt/Rac-dependent cytoskeletal reorganization, leading to constitutive Ca2+ entry and breast cancer cell migration (without affecting the development of metastasis), in a mouse model. We describe, for the first time, the biological role of a new alkyl-ether-lipid on TRPV2 channel trafficking in breast cancer cells and highlight the potential modulation of TRPV2 by alkyl-ether-lipids as a novel avenue for research in the treatment of metastatic cancer.
Document type :
Journal articles
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https://hal.univ-brest.fr/hal-03278876
Contributor : Nicolas Renard Connect in order to contact the contributor
Submitted on : Tuesday, July 13, 2021 - 10:02:49 AM
Last modification on : Wednesday, October 20, 2021 - 3:22:32 AM
Long-term archiving on: : Thursday, October 14, 2021 - 6:20:27 PM
Contributor : Nicolas Renard Connect in order to contact the contributor
Submitted on : Tuesday, July 13, 2021 - 10:02:49 AM
Last modification on : Wednesday, October 20, 2021 - 3:22:32 AM
Long-term archiving on: : Thursday, October 14, 2021 - 6:20:27 PM
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- Gueguinou_et al_2021_Synthetic Alkyl-Ether-lipid promotes TRPV2 Channel_suppl data.pdf Embargoed until : 2021-12-12
Identifiers
- HAL Id : hal-03278876, version 1
- DOI : 10.1016/j.ceca.2021.102435
Collections
UNIV-BREST | ISCR-CORINT | CEMCA-BREST | UNIV-RENNES | INSA-GROUPE | IBSAM | UR1-UFR-SPM | INC-CNRS | UNIV-NANTES | UNIV-RENNES1 | UNIV-TOURS | CNRS | UNIV-POITIERS | INSA-RENNES | ISCR | IMMUNO | STIM
Citation
Maxime Guéguinou, Romain Felix, Séverine Marionneau-Lambot, Thibauld Oullier, Aubin Penna, et al.. Synthetic alkyl-ether-lipid promotes TRPV2 channel trafficking trough PI3K/Akt-girdin axis in cancer cells and increases mammary tumour volume. Cell Calcium, Elsevier, 2021, 97, pp.102435. ⟨10.1016/j.ceca.2021.102435⟩. ⟨hal-03278876⟩
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