Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells.

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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https://hal-univ-tours.archives-ouvertes.fr/hal-01387061
Contributeur : Martin Soucé <>
Soumis le : mardi 25 octobre 2016 - 10:20:46
Dernière modification le : jeudi 11 janvier 2018 - 06:14:42

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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. 〈http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path=8122&pubmed-linkout=1〉. 〈10.18632/oncotarget.8122〉. 〈hal-01387061〉

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