3 years ago

Beyond the "lock and key" paradigm: targeting lipid rafts to induce the selective apoptosis of cancer cells.

Luciano Porto Kagami, Carolina de Miranda Silva, Gustavo Machado das Neves, Vera Lucia Eifler-Lima, Anna Carolina Schneider Alves, Reinaldo Antonio Dias, Fernando Cidade Torres, Daniel Fabio Kawano, Ivone Carvalho
For more than 40 years, the fluid mosaic model of cellular membranes have supported our vision of an inert lipid bilayer containing membrane protein receptors that are randomly hit by extracellular molecules to trigger intracellular signaling events. However, the notion that compartmentalized cholesterol- and sphingomyelin-rich membrane microdomains (known as lipid rafts) spatially arrange receptors and effectors to promote kinetically favorable interactions necessary for the signal transduction sounds much more realistic. Despite of their assumed importance for the dynamics of ligand-receptor interactions, lipid rafts and biomembranes as a whole remain less explored than the other classes of biomolecules because of the higher variability and complexity of their membrane phases, which rarely provide the detailed atomic-level structural data in X-ray crystallography assays necessary for molecular modeling studies. The fact that some alkylphospholipids (e.g. edelfosine: 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) selectively induces the apoptotic death of cancer cells by recruiting Fas death receptors and the downstream signaling molecules into clusters of lipid rafts suggests these potential drug targets deserve a more in-depth investigation. Herein we review the structure of lipid rafts, their role in apoptotic signaling pathways and their potential role as drug targets for the treatment of cancer.

Publisher URL: http://doi.org/10.2174/0929867325666180111100601

DOI: 10.2174/0929867325666180111100601

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