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Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells.
Audrey Gambade
1
Sami Zreika
2
Maxime Guéguinou
1
Igor Chourpa
3
Gaëlle Fromont
1, 4
Ana Maria Bouchet
1
J Burlaud-Gaillard
5
Marie Potier-Cartereau
1
Sébastien Roger
1
Vincent Aucagne
6
Stéphan Chevalier
1
Christophe Vandier
1
Caroline Goupille
4, 1
Günther Weber
1, *
*
Corresponding author
Audrey Gambade 1
Author
Sami Zreika 2
Mail :
Author
Maxime Guéguinou 1
Mail :
Author IdHAL : maxime-gueguinou
Igor Chourpa 3
Mail :
Author IdHAL : igor-chourpa
Gaëlle Fromont 1, 4
Author
Ana Maria Bouchet 1
Author
J Burlaud-Gaillard 5
Author
Marie Potier-Cartereau 1
Mail :
Author IdHAL : marie-potier-cartereau ORCID : https://orcid.org/0000-0002-1361-3397
Sébastien Roger 1
Author
Vincent Aucagne 6
Mail :
Author IdHAL : vincent-aucagne
Stéphan Chevalier 1
Author
Christophe Vandier 1
Mail :
Author
Caroline Goupille 4, 1
Author
Günther Weber 1
Mail :
Correspondent author
1
Inserm UMR1069 (France)
- 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
Jinan University, Tripoli, Lebanon (Lebanon)
3
NMNS - Nanomédicaments et Nanosondes, EA 6295 (Faculté de pharmacie
31 avenue Monge
37200 Tours - France)
- Université de Tours (60 rue du Plat d'Étain, 37020 Tours cedex 1 - France)
5
Université Francois Rabelais [Tours] (60 Rue du Plat d'Étain, 37000 Tours - France)
6
CBM - Centre de biophysique moléculaire (Rue Charles Sadron 45071 ORLEANS CEDEX 2 - France)
- UO - Université d'Orléans : UPR4301 (Château de la Source - Avenue du Parc Floral - BP 6749 - 45067 Orléans cedex 2 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UPR4301 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UPR4301 (France)
Abstract : Expression of the antimicrobial peptide hCAP18/LL-37 is associated to malignancy in various cancer forms, stimulating cell migration and metastasis. We report that LL-37 induces migration of three cancer cell lines by activating the TRPV2 calcium-permeable channel and recruiting it to pseudopodia through activation of the PI3K/AKT pathway. Ca2+ entry through TRPV2 cooperated with a K+ efflux through the BKCa channel. In a panel of human breast tumors, the expression of TRPV2 and LL-37 was found to be positively correlated. The D-enantiomer of LL-37 showed identical effects as the L-peptide, suggesting that no binding to a specific receptor was involved. LL-37 attached to caveolae and pseudopodia membranes and decreased membrane fluidity, suggesting that a modification of the physical properties of the lipid membrane bilayer was the underlying mechanism of its effects.
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Journal articles
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https://hal-univ-tours.archives-ouvertes.fr/hal-01387061
Contributor : Martin Soucé <>
Submitted on : Tuesday, October 25, 2016 - 10:20:46 AM
Last modification on : Tuesday, January 28, 2020 - 9:36:07 AM
Contributor : Martin Soucé <>
Submitted on : Tuesday, October 25, 2016 - 10:20:46 AM
Last modification on : Tuesday, January 28, 2020 - 9:36:07 AM
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- HAL Id : hal-01387061, version 1
- DOI : 10.18632/oncotarget.8122
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UNIV-TOURS | CNRS | CBM | INC-CNRS | UNIV-ORLEANS
Citation
Audrey Gambade, Sami Zreika, Maxime Guéguinou, Igor Chourpa, Gaëlle Fromont, et al.. Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells.. Oncotarget, Impact journals, 2016, 7 (17), pp.23785-23800. ⟨10.18632/oncotarget.8122⟩. ⟨hal-01387061⟩
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