Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis.

Autor:	Ackermann T; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.; School of Cancer Sciences, University of Glasgow, Glasgow, G611QH, UK., Shokry E; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK., Deshmukh R; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK., Anand J; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK., Galbraith LCA; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK., Mitchell L; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK., Rodriguez-Blanco G; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK., Villar VH; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.; School of Medicine, University of St Andrews, St. Andrews, KY16 9TF, UK., Sterken BA; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK., Nixon C; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK., Zanivan S; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.; School of Cancer Sciences, University of Glasgow, Glasgow, G611QH, UK., Blyth K; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.; School of Cancer Sciences, University of Glasgow, Glasgow, G611QH, UK., Sumpton D; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK., Tardito S; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. saverio.tardito@meduniwien.ac.at.; School of Cancer Sciences, University of Glasgow, Glasgow, G611QH, UK. saverio.tardito@meduniwien.ac.at.; Center for Cancer Research, Medical University of Vienna, Comprehensive Cancer Center, Vienna, 1090, Austria. saverio.tardito@meduniwien.ac.at.
Jazyk:	angličtina
Zdroj:	EMBO molecular medicine [EMBO Mol Med] 2024 Oct 21. Date of Electronic Publication: 2024 Oct 21.
DOI:	10.1038/s44321-024-00142-x
Abstrakt:	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 type of cell death caused by iron-dependent lipid peroxidation and counteracted by the antioxidant activity of the selenoprotein GPX4. 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 ferroptosis when forming colonies at low density. We found that secretion of the anti-ferroptotic factors, identified as monounsaturated fatty acid (MUFA) containing lipids, and the vulnerability to ferroptosis of single cells depends on the low expression of stearyl-CoA desaturase (SCD) that is proportional to cell density. Finally, we show that the inhibition of Sec-tRNAsec biosynthesis, an essential step for selenoprotein production, causes ferroptosis and impairs the lung seeding of circulating TNBC cells that are no longer protected by the MUFA-rich environment of the primary tumour. (© 2024. The Author(s).)
Databáze:	MEDLINE
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