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

Audrey Gambade; Sami Zreika; Maxime Guéguinou; Igor Chourpa; Gaëlle Fromont; Ana Maria Bouchet; J Burlaud-Gaillard; Marie Potier-Cartereau; Sébastien Roger; Vincent Aucagne; Stéphan Chevalier; Christophe Vandier; Caroline Goupille; Günther Weber

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

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Cancer

Complete list of metadatas

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 : Thursday, July 11, 2019 - 4:04:02 PM

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

Links full text

Identifiers

Collections

Citation

Export

Metrics

128

Contact

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

Links full text

Identifiers

Collections

Citation

Export

Share

Metrics

128

Contact