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Gambade A., Zreika S., Guéguinou M., Chourpa I., Fromont-Hankard G., Bouchet A. M., Burlaud-Gaillard J., Potier-Cartereau M., Roger S., Aucagne V., Chevalier S., Vandier C., Goupille C. and Weber G.

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

Oncotarget (2016) 7 (17) 23785-23800 - doi : 10.18632/oncotarget.8122

par Frapart - publié le , mis à jour le

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.