Fiche publication
Date publication
janvier 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DEVY Jérôme
,
Dr DUCA Laurent
,
Pr MARTINY Laurent
,
Pr DEVARENNE-CHARPENTIER Emmanuelle
,
Dr SALESSE Stéphanie
Tous les auteurs :
Ouchani F, Devy J, Rusciani A, Helesbeux JJ, Salesse S, Letinois I, Gras-Billart D, Duca L, Duval O, Martiny L, Charpentier E
Lien Pubmed
Résumé
BACKGROUND: Leukemic cell adhesion to proteins of the bone marrow microenvironment provides signals which control morphology, motility and cell survival. We described herein the ability of ethoxyfagaronine (etxfag), a soluble synthetic derivative of fagaronine, to prevent leukemic cell adhesion to fibronectin peptide (FN/V). METHODS: Phosphorylation of fak and pyk2 were evaluated by immunoblotting. Labelled proteins were localized by confocal microscopy. PI 3-kinase activity was evaluated by in vitro kinase assay. RESULTS: Subtoxic concentration of etxfag reduced L1210 cell adhesion to FN/V dependently of beta1 integrin engagement. Etxfag impaired FN-dependent formation of beta1 clustering without modifying beta1 expression at the cell membrane. This was accompanied by a decrease of focal adhesion number, a diminution of fak and pyk2 phosphorylation at Tyr-576, Tyr-861 and Tyr-579, respectively leading to their dissociations from beta1 integrin and inhibition of PI 3-kinase activity. Etxfag also induced a cell retraction accompanied by a redistribution of phosphorylated fak and pyk2 in the perinuclear region and lipid raft relocalization. CONCLUSION: Through its anti-adhesive potential, etxfag, combined with conventional cytotoxic drugs could be potentially designed as a new anti-leukemic drug.
Référence
Anal Cell Pathol (Amst). 2012;35(4):267-84
