From fat to fear: how lipid powers cancer spread

Metastasis and therapy resistance drive cancer-related deaths, with melanoma cells exhibiting phenotypic plasticity that allows them to switch between proliferative and invasive states. In this issue of Genes & Development, Chocarro-Calvo and colleagues (doi:10.1101/gad.351985.124) reveal that oleic acid activates AXL, a receptor involved in metastasis and therapy resistance, linking lipid metabolism to melanoma aggressiveness. They demonstrate that MITF^Low/AXL^High cells induce lipolysis in human adipose tissue via WNT5A secretion, compensating for lipid synthesis deficiencies. The study highlights distinct lipid uptake mechanisms in melanoma subpopulations and suggests that targeting AXL-driven lipid uptake could provide therapeutic opportunities. These findings have broad implications, indicating that metabolic cues influence AXL activation in other cancers.