Extended Data Fig. 1: Further characterization of LSD1/CoREST in breast cancer and long-term estrogen deprivation (LTED) model.
From: Endocrine resistance and breast cancer plasticity are controlled by CoREST
a, Kaplan–Meier survival curves segregated by ERα expression and TP53 mutation status (METABRIC dataset of 1,423 samples). Overall survival of patients with ER−/TP53 mutations is significantly diminished. P value was calculated using a log-rank (Mantel–Cox) test. b, CD24 and CD44 expression after 12 months (M) in LTED. c, FACS of T47D-LTED biological replicate (FM, full media). d, e, CD24 and CD44 expression in FM, TamR, FulR, and LTED T47D (d) and MCF7 (e). f, Growth curves of 2 × 105 FM and LTED T47D (3–9 M) cultured with DMSO (vehicle) or 1 µM tamoxifen or fulvestrant for 5 days, n = 3 biological independent replicates, data are presented as mean values + SEM, p-value < 0.001 (two-way ANOVA). g, Heatmap of 3,206 significantly downregulated genes (FC > 2, q-value < 0.05) during acquisition of resistance in T47D. Major transcriptomic changes occurred after 6 M in LTED. h, GSEA of 4 M and 6 M T47D-LTED cells. Basal breast cancer, EMT transition, and ductal invasive signatures were upregulated while response to estrogen and luminal breast cancer signatures were downregulated after 6 months in LTED conditions. NES, normalized enrichment score. i, Single-cell SNV (single nucleotide variant) analysis from 6 × 103 FM and 6 M T47D-LTED. No FM cells harboured BRAF or KRAS mutations while ~60% of 6M cells acquired mutations in both genes. j, RNA-seq signal at ESR1 and PGR in FM and 9M T47D-LTED.
