Tumor cell lipid rafts (LR) (LR)

Tumor cell lipid rafts are specialized, highly ordered microdomains within the plasma membrane that are enriched in cholesterol, sphingolipids, and specific scaffolding proteins like caveolins and flotillins (Greenlee et al., 2021, Cancers). These domains serve as critical platforms for the spatial organization of signaling molecules, facilitating the assembly of complexes that drive essential oncogenic processes such as cell proliferation, survival, and metastasis (Mollinedo & Gajate, 2015, Adv Biol Regul). In many cancers, lipid rafts are reorganized or overexpressed to enhance signaling through receptors like EGFR and HER2, while also providing a sanctuary for survival proteins to evade apoptosis (Patra, 2008, BBA). Because of their central role in maintaining the integrity of oncogenic signaling hubs, lipid rafts have emerged as a promising therapeutic target. Pharmacological agents, including alkylphospholipids like edelfosine and cholesterol-modulating compounds, can selectively disrupt these microdomains in tumor cells, leading to the inactivation of survival pathways and the induction of programmed cell death (Gajate & Mollinedo, 2014, Mol Pharm). This approach offers a unique mechanism to overcome conventional drug resistance by targeting the physical organization of the membrane itself.

Other names

Membrane microdomainsDetergent-resistant membranes (DRMs)Cholesterol-rich microdomainsLipid microdomainsLiquid-ordered phases

Disruption of membrane microdomain integrity through cholesterol depletion or lipid remodeling, leading to the dissociation of oncogenic signaling complexes and induction of apoptosis (Mollinedo & Gajate, 2015; Greenlee et al., 2021).