JAK-STAT signaling in inflammatory breast cancer enables chemotherapy-resistant cell states [RNA-seq]

We developed and characterized derivates of inflammatory breast cancer (IBC) cell lines resistant to paclitaxel and doxorubicin to mimic therapeutic resistance in patients. Comprehensive molecular characterization of gene expression, genetic, epigenetic, and metabolomic profiles of parental and resistant cells revealed a central role for STAT3 in regulating genes associated with inflammation and resistance to chemotherapy, which we also validated in clinical patient samples. Our results suggest a combination of chemotherapy with inhibition of JAK/STAT signaling could be a more effective therapeutic strategy in IBC. RNA-seq: Gene expression analysis of SUM149 and FCIBC02 Parental, Paclitaxel-Resistant, and Doxorubicin-resistant cell lines. Cells were treated with either vehicle or the indicated drug combinations of Paclitaxel, Doxorubicin, and INC424. SUM149 Paclitaxel-resistant cells were also sorted for EpCAM high and low populations and treated with either vehicle or Paclitaxel. All samples were sequenced in duplicates.