期刊
ONCOTARGET
卷 7, 期 17, 页码 23785-23800出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8122
关键词
LL-37; calcium signaling; membrane association; cell migration; breast cancer
资金
- Region Centre-Val de Loire
- University of Tours, INSERM
- Ligue Contre le Cancer
- ARD2020 Biomedicaments
- Ministere de l'Enseignement Superieur et de la Recherche
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.
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