FGFR1 associates with gene promoters and regulates gene transcription: Implications for endocrine resistance in ER+/FGFR1-amplified breast cancer [CAMA1_ChIP-Seq]

Using ChIP-Seq analysis of ER+/FGFR1-amplified breast cancer cells and PDXs, we found FGFR1 occupancy at transcription start sites with high overlap with histone modifications associated with active gene transcription. Mass spectrometry analysis of the nuclear and chromatin-bound FGFR1 interactome identified RNA-Polymerase II (Pol II) and FOXA1, with FOXA1 silencing impairing FGFR1 recruitment to chromatin. Transduction of FGFR1(SP-)(NLS) into MCF7 cells resulted in overexpression of nuclear FGFR1 and resistance to antiestrogens. Finally, an expression signature associated with nuclear FGFR1 correlated with endocrine resistance in patients treated with antiestrogens Overall design: Examination of FGFR1 genomic distribution in CAMA1 stimulated with FGF2 5 ng/ml ± Erdafitinib 250 nM for 3 h breast cancer cells. Two replicates were used