Cancer cell plasma membrane lipid raft microdomain (LR)

Lipid rafts are specialized, highly ordered microdomains within the plasma membrane lipid bilayer, enriched in cholesterol, sphingolipids, and specific proteins like caveolins and flotillins (Mollinedo & Gajate, 2015). In cancer cells, these microdomains are often more abundant or altered in composition, serving as critical platforms for the assembly and activation of pro-survival and pro-migratory signaling pathways, including the PI3K/Akt and MAPK pathways (Patra, 2008). Targeting these structures, a strategy known as membrane lipid therapy, aims to disrupt the spatial organization of oncogenic receptors and signaling molecules (Li et al., 2022). Drugs such as synthetic alkylphospholipids, including edelfosine and miltefosine, selectively accumulate in cancer cell rafts, inducing apoptosis by displacing survival signals or recruiting death receptors like Fas/CD95 (Gajate & Mollinedo, 2014). While promising for overcoming multidrug resistance, the therapeutic challenge lies in achieving high selectivity for malignant rafts over those in healthy cells to minimize systemic toxicity (Greenlee et al., 2021).

Other names

Lipid raftsDetergent-resistant membranesMembrane microdomainsCholesterol-rich microdomainsLiquid-ordered domains

Disruption of membrane microdomain structural integrity, depletion of membrane cholesterol, and displacement of oncogenic signaling proteins from the plasma membrane to induce apoptosis.