“Lipid raft reorganization” refers to the dynamic changes in the composition and structure of lipid rafts within cell membranes. Lipid rafts are specialized microdomains within the cell membrane that are rich in cholesterol, sphingolipids, and specific proteins. These rafts play a crucial role in various cellular processes, including signal transduction, membrane trafficking, and cell adhesion.

The reorganization of lipid rafts involves alterations in the distribution and clustering of lipids and proteins within these microdomains. This process is often associated with changes in cell signaling and responses to external stimuli. Lipid rafts can be influenced by various factors, including the presence of specific molecules, cellular stress, or the activation of signaling pathways.

Alonso-Pérez et al. examined the effect of edelfosine on metastatic colonization and angiogenesis. Using non-invasive bioluminescence imaging and histological examination, they found that oral administration of edelfosine in nude mice significantly inhibited the lung and brain colonization of luciferase-expressing 435-Lung-eGFP-CMV/Luc metastatic cells, resulting in prolonged survival. In metastatic 435-Lung and MDA-MB-231 breast cancer cells, they found that edelfosine also inhibited cell adhesion to collagen-I and laminin-I substrates, cell migration in chemotaxis and wound-healing assays, as well as cancer cell invasion. In 435-Lung and other MDA-MB-435-derived sublines with different organotropism, edelfosine induced G2/M cell cycle accumulation and apoptosis in a concentration- and time-dependent manner. Edelfosine also inhibited in vitro angiogenesis in human and mouse endothelial cell tube formation assays. The antimetastatic properties were specific to cancer cells, as edelfosine had no effects on viability in non-cancerous cells. Edelfosine accumulated in membrane rafts and endoplasmic reticulum of cancer cells, and membrane raft-located CD44 was downregulated upon drug treatment. Taken together, this study highlights the potential of edelfosine as an attractive drug to prevent metastatic growth and organ colonization in cancer therapy. The raft-targeted drug edelfosine displays a potent activity against metastatic organ colonization and angiogenesis, two major hallmarks of tumor malignancy ¹⁾