Lipid raft (membrane microdomain)

Lipid rafts are cholesterol- and sphingolipid-enriched microdomains in the plasma membrane that organize the spatial distribution and function of signaling proteins. In cancer, tumor cells display increased abundance and altered composition of lipid rafts, which act as platforms for oncogenic signaling pathways (e.g., PI3K/AKT), survival, proliferation, apoptosis resistance, migration, and metastasis. Disruption of lipid rafts, especially through cholesterol depletion or direct modulation, can inhibit tumor cell signaling, induce cell death by clustering death receptors (such as Fas/CD95 or TRAIL receptors), and increase sensitivity to anticancer drugs. Pharmacological targeting of rafts, either by depleting membrane cholesterol, inhibiting raft-associated enzymes, or using synthetic agents that recruit death receptors to rafts, is an emerging therapeutic strategy in oncology. However, challenges remain due to potential toxicities stemming from the fundamental roles of rafts in healthy tissue.

Other names

Membrane raftsMembrane microdomainsCholesterol-rich domainsLipid microdomainsRaft domains

Disruption of lipid raft integrity to inhibit survival signaling; Induction of formation of raft-associated death receptor complexes (e.g., CASMER) to promote apoptosis; Inhibition of cholesterol synthesis to reduce raft-mediated signaling and tumor progression