Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells. - Archive ouverte HAL Access content directly
Journal Articles Oncotarget Year : 2016

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

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Sami Zreika
  • Function : Author
  • PersonId : 859603
Igor Chourpa
Vincent Aucagne
Christophe Vandier
  • Function : Author
  • PersonId : 917978

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.

Dates and versions

hal-01387061 , version 1 (25-10-2016)

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Cite

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, 2016, 7 (17), pp.23785-23800. ⟨10.18632/oncotarget.8122⟩. ⟨hal-01387061⟩
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