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

Autor:	Gambade A; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France., Zreika S; Department of Medical Lab Technology, Jinan University, Tripoli, Lebanon., Guéguinou M; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.; Ion Channel Network Canceropole Grand Ouest, Nantes, France., Chourpa I; Université François Rabelais, Tours, France., Fromont G; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.; Ion Channel Network Canceropole Grand Ouest, Nantes, France.; CHRU Hôpital Bretonneau, Tours, France., Bouchet AM; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.; Ion Channel Network Canceropole Grand Ouest, Nantes, France., Burlaud-Gaillard J; Université François Rabelais, Tours, France., Potier-Cartereau M; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.; Ion Channel Network Canceropole Grand Ouest, Nantes, France., Roger S; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France., Aucagne V; Centre de Biophysique Moléculaire, CNRS UPR 4301, Orléans, France., Chevalier S; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France., Vandier C; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.; Ion Channel Network Canceropole Grand Ouest, Nantes, France., Goupille C; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.; CHRU Hôpital Bretonneau, Tours, France., Weber G; Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.; Université François Rabelais, Tours, France.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2016 Apr 26; Vol. 7 (17), pp. 23785-800.
DOI:	10.18632/oncotarget.8122
Abstrakt:	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. Competing Interests: All of authors declare that they have no competing interests.
Databáze:	MEDLINE
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