title: 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.
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gambade
authors.affiliation: Department of Medical Lab Technology, Jinan University, Tripoli, Lebanon.
authors.forename: Sami
authors.initials: S
authors.lastname: Zreika
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.|Ion Channel Network Canceropole Grand Ouest, Nantes, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Guéguinou
authors.affiliation: Université François Rabelais, Tours, France.
authors.forename: Igor
authors.initials: I
authors.lastname: Chourpa
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.|Ion Channel Network Canceropole Grand Ouest, Nantes, France.|CHRU Hôpital Bretonneau, Tours, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Fromont
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.|Ion Channel Network Canceropole Grand Ouest, Nantes, France.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Bouchet
authors.affiliation: Université François Rabelais, Tours, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Burlaud-Gaillard
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.|Ion Channel Network Canceropole Grand Ouest, Nantes, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Potier-Cartereau
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Roger
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, Orléans, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Aucagne
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Chevalier
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.|Ion Channel Network Canceropole Grand Ouest, Nantes, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vandier
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.|CHRU Hôpital Bretonneau, Tours, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Goupille
authors.affiliation: Inserm, UMR1069, Nutrition, Croissance et Cancer, Tours, France.|Université François Rabelais, Tours, France.
authors.forename: Günther
authors.initials: G
authors.lastname: Weber
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D014408:Biomarkers, Tumor; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; D002118:Calcium; D054804:Cathelicidins
keywords: LL-37; breast cancer; calcium signaling; cell migration; membrane association