Oxidative Phosphorylation Is a Metabolic Vulnerability of Endocrine Therapy-Tolerant Persister Cells in ER+ Breast Cancer.

ABSTRACT: Despite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retain tumor-forming potential. Therefore, strategies targeting such persister cells may prevent recurrent disease. Using CRISPR-Cas9 genome-wide knockout screening in ER+ breast cancer cells, we identified a survival mechanism involving metabolic reprogramming with reliance upon mitochondrial respiration in endocrine-tolerant persister cells. Quantitative proteomic profiling showed reduced levels of glycolytic proteins in persisters. Metabolic tracing of glucose revealed an energy-depleted state in persisters, in which oxidative phosphorylati

SUBMITTER: Tau S 

PROVIDER: S-EPMC11908958 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature