GSE168644
Endocrine resistance and breast cancer plasticity are controlled by CoREST
Using a new model system to track evolution of resistance from ER+ to ER-, we show that the LSD1/CoREST complex is a key determinant for luminal-to-basal reprogramming independently on LSD1's enzymatic activity. Overall design: RNAseq experiments of T47D cells grown in estrogen deprived conditions for 3 days and up to 8 months. RNAseq experiments in T47D cells and long term estrogen deprived conditions after LSD1 KO using CRISPR/Cas9 as well as treatment with  LSD1/CoREST inhibitors SP2509 and Corin. ChIPseq of LSD1/ H3K27ac during resistance evolution (T47D cells in media with estrogen and estrogen deprived (LTED6M, LTED6M CD44 sorted cells and LTED9M)). ChIPseq of ERa, FOXA1, RCOR1, RNApol in T47D cells and RCOR1/SMARCC1/cjun, RNApolII, H3K4me2 in estrogen deprived cells for 9 months or fully reprogrammed cells. LSD1, cjun ChIPseq in T47D cells fully reprogrammed after stable knockdown of cjun. LSD1, cjun, H4K4me2 ChIPseq in fully reprogrammed cells with LSD1 KO by CRISPR/Cas9 . ATACseq in Parental T47D cells with wildtype LSD1 or knockout. ATACseq in reprogrammed cells with wildtype LSD1 or knockout as well as LSD1 knockdown and rescue with wildtype LSD1 or catalytic dead mutant. H3K4me1 and H3K27ac CUT and RUN experiment performed in the same samples used for ATACseq. LSD1 ChIPseq from fresh tissue from a patient that develop recurrent tumor after 5 years of tamoxifen treatment