STIM1 Mediates Calcium-dependent Epigenetic Reprogramming in Pancreatic Cancer [ChIPseq_siSTIM1_Thap]

We characterized Gemcitabine resistant pancreatic cancer tumors and show that the co-amplification of RRM1 and STIM1 confers novel and independent properties to gemcitabine resistant cells. The upregulation of RRM1 drives gemcitabine resistance, while the amplification of STIM1 leads to increased cytosolic calcium upon stress, eliciting ER stress resistance and NFAT activation. Overall design: We performed ChIPseq in L3.6pl (Par) and gemcitabine resistant L3.6pl cells (GemR) depleted of STIM1 and treated with 500nM thapsigargin. For this, Par were treated with siControl (siCont) and with DMSO (Veh) or 500nM thapsigargin (Thap), while GemR were depleted or not of STIM1 (siCont or siSTIM1) and treated either with DMSO (Veh) or with 500nM thapsigargin (Thap). The siRNA mediated depletion was perfomed for 48h, while the thapsigargin treatment lasted for 3h. H3K27ac ChIPseq was performed for all conditions, while ATF4 ChIPseq was only generated for thapsigargin treated Par.