title: Lipid rafts in anticancer therapy: Theory and practice (Review).
abstract: To enlarge and stabilize transient raft patterns, proteins interact with membrane lipids. By lateral movements, these small lipid rafts (LRs) may coalesce into large platforms (raft clusters), allowing the alignment of transmembrane proteins that easily crosslink. The formation of raft clusters permits TNFR superfamily membrane receptors of the Lo phase to subsequently cooperate with transducer and adaptor proteins to create receptosomes and/or signalosomes, even without external ligand binding. Chemical agents that disrupt actin and/or the microtubular network were also found to facilitate the death signal through the known death cascades. Hence, death machinery is triggered to initiate, transmit and execute the apoptosis (extrinsic and/or intrinsic) of tumor cells. Certain anticancer drugs such as edelfosine and aplidin convey these death signals, suggesting a disregard for the necessity of ligand-receptor communication. This also stresses the importance of existing LRs in tumor cells as a prerequisite for improving the strategies of anticancer therapies based on their physical and biochemical modifications. Tumor cells ignore the natural mechanisms of their elimination. As a result, the cytokines of the TNFR superfamily are unable to induce a physiological response guiding cells to programmed cell death. The clustering of LRs provides the opportunity to overcome the resistance of tumor cells to death ligand-induced apoptosis, thus offering a less harmful alternative, as well as a more efficient strategy, for eliminating tumor cells.
authors.affiliation: Department of Cell Ultrastructure, Medical Research Center, Polish Academy of Sciences, 02-106 Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Pajak
authors.forename: Urszula
authors.initials: U
authors.lastname: Wojewódzka
authors.forename: Barbara
authors.initials: B
authors.lastname: Gajkowska
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Orzechowski