Metabolic perturbations sensitize triple-negative breast cancers to apoptosis induced by BH3 mimetics
Veerle W. Daniëls, Jason J. Zoeller, Nick van Gastel, Kelley E. McQueeney, Salma Parvin, Danielle S. Potter, Geoffrey Fell, Vinícius Guimarães Ferreira, Binyam Yilma, Rajat Gupta, Johan Spetz, Patrick Bhola, Jennifer E. Endress, Isaac S. Harris, Emanuel Carrilho, Kristopher A. Sarosiek, David T. Scadden, Joan S. Brugge, Anthony Letai
Abstract
concentrations below a critical threshold that resulted in depletion of adenine, which was the metabolic trigger that primed TNBC cells for apoptosis. These findings demonstrate a close interaction between metabolic and mitochondrial apoptotic signaling pathways and reveal that exploitation of a tumor-specific metabolic vulnerability can sensitize some TNBC to BH3 mimetics.
Topics & Concepts
Triple-negative breast cancerApoptosisCancer researchBreast cancerProgrammed cell deathChemistryCancerCell biologyBiologyMedicineInternal medicineBiochemistryCancer, Hypoxia, and MetabolismEpigenetics and DNA MethylationRNA modifications and cancer