Squalene accumulation in cholesterol auxotrophic lymphomas prevents oxidative cell death.

ABSTRACT: Cholesterol is essential for cells to grow and proliferate. Normal mammalian cells meet their need for cholesterol through its uptake or de novo synthesis¹, but the extent to which cancer cells rely on each of these pathways remains poorly understood. Here, using a competitive proliferation assay on a pooled collection of DNA-barcoded cell lines, we identify a subset of cancer cells that is auxotrophic for cholesterol and thus highly dependent on its uptake. Through metabolic gene expression analysis, we pinpoint the loss of squalene monooxygenase expression as a cause of cholesterol auxotrophy, particularly in ALK⁺ anaplastic large cell lymphoma (ALCL) cell lines and primary tumours. Squalene monooxygenase catalyses the oxidation of squalene to 2,3-oxidosqualene in t

SUBMITTER: Garcia-Bermudez J 

PROVIDER: S-EPMC6405297 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature