Paracrine secretion of monounsaturated fatty acids prevents ferroptosis in triple negative breast cancer and reveals selenocysteine synthesis dependency for metastatic seeding.

ABSTRACT: The limited availability of therapeutic options for patients with triple-negative breast cancer (TNBC) contributes to the high rate of metastatic recurrence and poor prognosis. Ferroptosis is a cell death caused by iron-dependent lipid peroxidation counteracted by the antioxidant activity of selenoproteins. Here, we show that TNBC cells secrete an anti-ferroptotic factor in the extracellular environment when cultured at high cell densities but are primed to when forming colonies from single cells. We found that the secretion of the anti-ferroptotic factor, identified as monounsaturated fatty acids (MUFA) containing lipids, and the vulnerability to ferroptosis of single cells depend on the expression of stearyl-CoA desaturase (SCD) that is proportional to cell density. Finally, we show that the inhibition of tRNAsec selenocysteinilation, an essential step for selenoproteins production, causes ferroptosis and impairs the lung seeding of circulating TNBC cells no longer protected by the MUFA-rich environment of the primary tumour.

INSTRUMENT(S): Q Exactive Plus, 7000A Triple Quadrupole GC/MS

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Saverio Tardito   David Sumpton  

PROVIDER: MSV000094784 | MassIVE | Fri May 17 02:34:00 BST 2024

REPOSITORIES: MassIVE