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Lipid rafts are specialized, highly ordered microdomains within the plasma membrane, characterized by an enrichment of cholesterol, sphingolipids, and specific scaffolding proteins such as caveolins and flotillins (Mollinedo & Gajate, 2015). In malignant cells, these rafts are often more abundant and serve as critical platforms for the assembly and activation of oncogenic signaling complexes, including the PI3K/Akt and Ras/MAPK pathways (Li et al., 2022). They facilitate cancer cell survival, proliferation, and metastasis by organizing receptors and downstream effectors into efficient signaling hubs (Patra, 2008). Furthermore, lipid rafts are involved in the regulation of apoptosis, often sequestering death receptors or facilitating their clustering upon stimulation (Gajate & Mollinedo, 2014). Therapeutic strategies targeting these domains involve the use of alkylphospholipids, which accumulate in rafts and induce apoptosis, or cholesterol-depleting agents that dismantle the raft structure (Mollinedo & Gajate, 2020). Consequently, lipid rafts represent a promising target for disrupting the fundamental survival mechanisms of cancer cells while potentially enhancing the efficacy of other anti-cancer treatments.
Disruption of membrane microdomain integrity, depletion of membrane cholesterol, and displacement of oncogenic signaling proteins from the plasma membrane.
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