Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway.

ABSTRACT: Plasticity of the cell state has been proposed to drive resistance to multiple classes of cancer therapies, thereby limiting their effectiveness. A high-mesenchymal cell state observed in human tumours and cancer cell lines has been associated with resistance to multiple treatment modalities across diverse cancer lineages, but the mechanistic underpinning for this state has remained incompletely understood. Here we molecularly characterize this therapy-resistant high-mesenchymal cell state in human cancer cell lines and organoids and show that it depends on a druggable lipid-peroxidase pathway that protects against ferroptosis, a non-apoptotic form of cell death induced by the build-up of toxic lipid peroxides. We show that this cell state is characterized by activity of enzymes that promo

SUBMITTER: Viswanathan VS 

PROVIDER: S-EPMC5667900 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature