Glycosaminoglycan-driven lipoprotein uptake protects tumours from ferroptosis.

ABSTRACT: Lipids are essential components of cancer cells due to their structural and signalling roles¹. To meet metabolic demands, many cancers take up extracellular lipids^2-5; however, how these lipids contribute to cancer growth and progression remains poorly understood. Here, using functional genetic screens, we identify uptake of lipoproteins-the primary mechanism for lipid transport in circulation-as a key determinant of ferroptosis sensitivity in cancer. Lipoprotein supplementation robustly inhibits ferroptosis across diverse cancer types, primarily through the delivery of α-tocopherol (α-toc), the most abundant form of vitamin E in human lipoproteins. Mechanistically, cancer cells take up lipoproteins through a pathway dependent on sulfated glycosaminoglycans (GAGs) lin

SUBMITTER: Calhoon D 

PROVIDER: S-EPMC12320555 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature