Amino acids availability and subsequent metabolic reprogramming sustain endocrine resistance in breast cancer (mRNA)

The majority of breast tumours express oestrogen receptor (ER) and receive endocrine therapy (ET) as standard care. Despite its efficacy, ~40% of women relapse with endocrine therapy-resistant (ETR) disease. A global transcription analysis and subsequent integrative approaches of ETR cells showed a deregulated node between miR-23b-3p and the amino acids transporter SLC6A14. Mechanistic analysis supports a model in which such deregulation impairs amino acids metabolism in the ETR cells with subsequent activation of autophagy and enhanced aspartate and glutamate import mediated by the SLC1A2 transporter. The clinical significance of these findings was validated by multiple orthogonal approaches in a large cohort of ET-treated patients, in patient-derived xenografts and in in vivo experiments. Targeting such reprogramming impairs the aggressive features of ETR cells and offers predictive biomarkers and potential targetable pathways to be exploited to combat or delay ETR in ER positive breast cancers. This dataset consist in 9 samples obtained from 3 independent RNA extactions of parental cell line MCF7 (model of breast adenocarcinoma), in presence (MCF7+E2) or absence (MCF7-E2) of oestrogen (E2), and their derivative LTED (Long Term Estrogen Deprived)