title: Localization of Fas/CD95 into the lipid rafts on down-modulation of the phosphatidylinositol 3-kinase signaling pathway.
abstract: Activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is known to protect tumor cells from apoptosis and more specifically from the Fas-mediated apoptotic signal. The antitumoral agent edelfosine sensitizes leukemic cells to death by inducing the redistribution of the apoptotic receptor Fas into plasma membrane subdomains called lipid rafts. Herein, we show that inhibition of the PI3K signal by edelfosine triggers a Fas-mediated apoptotic signal independently of the Fas/FasL interaction. Furthermore, similarly to edelfosine, blockade of the PI3K activity, using specific inhibitors LY294002 and wortmannin, leads to the clustering of Fas whose supramolecular complex is colocalized within the lipid rafts. These findings indicate that the antitumoral agent edelfosine down-modulates the PI3K signal to sensitize tumor cells to death through the redistribution of Fas into large platform of membrane rafts.
authors.affiliation: Centre National de la Recherche Scientifique-Unite Mixte de Recherche 5164, 33076 Bordeaux, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Bénéteau
authors.forename: Mathieu
authors.initials: M
authors.lastname: Pizon
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chaigne-Delalande
authors.forename: Sophie
authors.initials: S
authors.lastname: Daburon
authors.forename: Patrick
authors.initials: P
authors.lastname: Moreau
authors.forename: Francesca
authors.initials: F
authors.lastname: De Giorgi
authors.forename: François
authors.initials: F
authors.lastname: Ichas
authors.forename: Amélie
authors.initials: A
authors.lastname: Rebillard
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Dimanche-Boitrel
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.forename: Patrick
authors.initials: P
authors.lastname: Legembre
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010742:Phospholipid Ethers / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010742:Phospholipid Ethers; D051057:Proto-Oncogene Proteins c-akt; D019014:fas Receptor; C026659:edelfosine