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
1 Inserm UMR1069
N2C - Nutrition, croissance et cancer (U 1069)
2 Jinan University, Tripoli, Lebanon
3 NMNS - Nanomédicaments et Nanosondes, EA 6295
4 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
5 Université Francois Rabelais [Tours]
6 CBM - Centre de biophysique moléculaire
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.
Keywords : LL-37 breast cancer calcium signaling cell migration membrane association
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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 : Monday, December 2, 2019 - 1:30:03 PM

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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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