PMID- 34167050 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240222 IS - 1532-1991 (Electronic) IS - 0143-4160 (Linking) VI - 97 DP - 2021 Jun 12 TI - Synthetic alkyl-ether-lipid promotes TRPV2 channel trafficking trough PI3K/Akt-girdin axis in cancer cells and increases mammary tumour volume. PG - 102435 LID - S0143-4160(21)00089-0 [pii] LID - 10.1016/j.ceca.2021.102435 [doi] AB - The Transient Receptor Potential Vanilloid type 2 (TRPV2) channel is highly selective for Ca(2+) 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 Ca(2+) -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 Ca(2+) 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 Ca(2+) 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. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Gueguinou, Maxime AU - Gueguinou M AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France; PATCH Team, EA 7501 GICC, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Felix, Romain AU - Felix R AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Marionneau-Lambot, Severine AU - Marionneau-Lambot S AD - Therassay Module 8, IRS-UN, Universite de Nantes, F-4400, France. FAU - Oullier, Thibauld AU - Oullier T AD - Inserm UMR 1235 TENS, Faculte de Medecine, Universite de Nantes, F-44035, France. FAU - Penna, Aubin AU - Penna A AD - STIM Team, ERL CNRS 7349, UFR SFA Pole Biologie Sante, Universite de Poitiers, F-86073, France. FAU - Kouba, Sana AU - Kouba S AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Gambade, Audrey AU - Gambade A AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Fourbon, Yann AU - Fourbon Y AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Ternant, David AU - Ternant D AD - PATCH Team, EA 7501 GICC, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Arnoult, Christophe AU - Arnoult C AD - PATCH Team, EA 7501 GICC, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Simon, Gaelle AU - Simon G AD - Univ. Brest, CNRS, CEMCA UMR 6521, 6 Avenue Victor Le Gorgeu, Brest, F-29238, France. FAU - Bouchet, Ana Maria AU - Bouchet AM AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Chantome, Aurelie AU - Chantome A AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Harnois, Thomas AU - Harnois T AD - STIM Team, ERL CNRS 7349, UFR SFA Pole Biologie Sante, Universite de Poitiers, F-86073, France. FAU - Haelters, Jean-Pierre AU - Haelters JP AD - Univ. Brest, CNRS, CEMCA UMR 6521, 6 Avenue Victor Le Gorgeu, Brest, F-29238, France. FAU - Jaffres, Paul-Alain AU - Jaffres PA AD - Univ. Brest, CNRS, CEMCA UMR 6521, 6 Avenue Victor Le Gorgeu, Brest, F-29238, France. FAU - Weber, Gunther AU - Weber G AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Bougnoux, Philippe AU - Bougnoux P AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Carreaux, Francois AU - Carreaux F AD - UMR CNRS 6226, Institut des Sciences Chimiques de Rennes, Universite de Rennes, F-35700, France. FAU - Mignen, Olivier AU - Mignen O AD - Inserm UMR 1227 Immunotherapies et Pathologies Lymphocytaires B, CHU Morvan, Universite de Bretagne Occidentale, Brest, F-29609, France. FAU - Vandier, Christophe AU - Vandier C AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. FAU - Potier-Cartereau, Marie AU - Potier-Cartereau M AD - Inserm UMR 1069, Nutrition Croissance Cancer, Faculte de Medecine, Universite de Tours, F-37032, France. Electronic address: marie.potier-cartereau@univ-tours.fr. LA - eng PT - Journal Article DEP - 20210612 PL - Netherlands TA - Cell Calcium JT - Cell calcium JID - 8006226 SB - IM OTO - NOTNLM OT - Alkyl-ether-lipid OT - Breast cancer cell migration OT - Constitutive Ca(2+) entry OT - TRPV2 EDAT- 2021/06/25 06:00 MHDA- 2021/06/25 06:01 CRDT- 2021/06/24 20:26 PHST- 2021/03/16 00:00 [received] PHST- 2021/06/09 00:00 [revised] PHST- 2021/06/10 00:00 [accepted] PHST- 2021/06/25 06:01 [medline] PHST- 2021/06/25 06:00 [pubmed] PHST- 2021/06/24 20:26 [entrez] AID - S0143-4160(21)00089-0 [pii] AID - 10.1016/j.ceca.2021.102435 [doi] PST - aheadofprint SO - Cell Calcium. 2021 Jun 12;97:102435. doi: 10.1016/j.ceca.2021.102435.